| Symptoms Seen in Thrombocytopenia If a platelet count is less than 30 x 109/L , bruising, petechiae, and purpura may be observed. Petechiae are small pinpoint hemorrhages (circled in red on the image) and purpura are larger purplish skin leaks (circled in blue on the image). Epistaxis may also be reported as well as gingival (gum) bleeding. Bleeding into the central nervous system may occur if the platelet count falls below 10 x 109/L . | View Page |
| Which of the following is a clinical symptom that is associated with thrombocytopenia? | View Page |
| Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syndrome Thrombotic thrombocytopenic purpura (TTP) is an uncommon, but very serious consumptive platelet disorder. Its cause is unknown, but there are several possible precipitating factors including infection, carcinoma, and pregnancy. More women than men are affected by TTP. If left untreated, the mortality rate is in excess of 90% due to multiorgan failure. Hemolytic uremic syndrome (HUS) is also a platelet consumptive disorder. HUS is thought by some to be the same condition as TTP because both disorders have the same underlying pathology. However, HUS is more often associated with renal failure and TTP with neurological manifestations including visual impairment, weakness, headache, dizziness, disorientation. seizures, or coma. Microangiopathic hemolytic anemia, thrombocytopenia, and fever is associated with both TTP and HUS. The patient's condition can deteriorate rapidly while these symptoms are becoming evident. HUS is usually seen in children; it is the most common cause of acute renal failure in children. Patients may have bloody diarrhea and symptoms resembling colitis. Diarrhea-related HUS is usually associated with ingestion of undercooked beef contaminated with Ecoli O157:H7; it is the Shiga-like toxin from this serotype that causes the illness. Some patients may have long term kidney dysfunction as a result ofthis virulent infection. For patients who have experienced renal failure, dialysis may be required. | View Page |
| Chronic Idiopathic Thrombocytopenic Purpura Chronic ITP occurs most often in females who are 20 - 40 years of age. Platelet counts usually range between 30 - 50 x 109/L and patients may or may not be symptomatic. Symptoms, when they occur, may include epistaxis and ecchymoses.Autoantibodies that are directed toward epitopes on GP IIb/IIIa or GP IIb/IX are detected in about 50 - 80% of patients with chronic ITP. | View Page |
| Treatment for ITP Treatment guidelines recommend that patients receive treatment if they have any of the following: Significant bleeding risk <20 x 109/L platelets and moderate bleeding <10 x 10 9/L platelets with no bleeding symptomsCorticosteroids are effective treatments for 50 - 80% of individuals with either acute or chronic ITP. Even with a reduction or discontinuation of corticosteroid treatment, remission can be maintained.Anti-D immunoglobulin, administered intravenously, may be an effective treatment for Rh-positive children or adults diagnosed with acute or chronic ITP. Anti-D immunoglobulin forms red blood cell complexes that block the destruction of platelets. This treatment cannot be used for patients who are Rh-negative or who have undergone a splenectomy. When a patient is refractory to the above treatments, other treatment possibilities include thrombopoietic drugs to stimulate the megakaryoblast or Rituximab, a treatment that targets CD 20-positive B-cells.Splenectomy may be a last resort treatment for chronic ITP sufferers if their platelet counts are below 30 x 109/ L or if symptoms warrant it. In ITP, antibodies develop that coat the platelets. The spleen produces macrophages whose Fc receptors recognize and destroy these antibody-coated platelets. Removing the spleen would decrease platelet destruction, but it is a last resort since the immunologic function of the spleen would also be lost. | View Page |
| Clinical Findings Clinical symptoms associated with DIC are: Extensive ecchymoses Petechiae Hemorrhage Ultimately, organ failure | View Page |
| Introduction Each year in the US alone, over one million individuals are diagnosed with an acute myocardial infarction (AMI) and approximately one half of these have had an AMI in the past. The incidence of congestive heart failure (CHF) is on the rise. It is the leading cause of hospitalization in those age 65 and older. Healthcare costs for cardiovascular disease (CVD), which includes coronary artery disease (CAD) and coronary heart disease (CHD) are more than $400 billion each year. Heart disease is currently the leading cause of death in the US. As many as 1% to 5% of patients with an AMI are misdiagnosed in the emergency department and are discharged. The laboratory's role is especially important in individuals with an AMI who present with AMI symptoms but have a nondiagnostic electrocardiogram (ECG). | View Page |
| History In the past, an AMI was primarily diagnosed by evaluating symptoms at patient presentation, ECG measurement, and results of enzyme assays that were considered cardiac enzymes. The enzymes, creatine kinase (CK), lactate dehydrogenase (LD), and aspartate aminotransferase (AST) were assayed several times a day often for several days to observe peak concentration and return to normal level for each enzyme. The first assay result was the baseline level or baseline concentration. Isoenzymes of CK and LD were later added for AMI diagnosis. All three of these enzymes are found in other tissues, making the diagnosis difficult and lengthy. In the 1980s, CK isoenzyme, CK-MB, though not totally cardiac specific, became the benchmark marker for an AMI. None of these enzymes are in any of the current recommendations except for CK-MBCurrent diagnosis, monitoring, and screening relating to heart disease includes measurement of lipids, proteins, enzymes, and other biomolecules. Risk stratification for cardiac and vascular disease is an additional role for measurement of these analytes. The physiological changes in the development of heart disease are better understood and the role of the clinical laboratory is greatly expanded.Today's markers are significant because of their location in the myocyte, the kinetics of their release in myocyte damage, and their rate of clearance from peripheral blood. | View Page |
| Use of Troponins Both cTnI and cTnT are cardiac specific, rapidly released after injury, remain in circulation for several days, normally in low concentration in serum or plasma, and can be rapidly assayed at relatively low cost.Currently cTnI and cTnT are considered the best markers in diagnosing ACS. Either protein is assayed to detect an AMI or other myocardial injury. These markers are especially helpful when the patient with chest pain and symptoms of an AMI does not have a diagnostic ECG. Cardiac troponin levels are used in risk stratification for a patient with chest pain that is not diagnosed with an AMI at presentation. Elevations of cardiac troponins are especially significant when other markers are normal. These elevations predict higher risk of severe cardiac events in the coming month. In other patients with ACS, troponin elevations identify those who are at risk for cardiac events for up to six months. | View Page |
| CK-MB Before troponins were used in cardiac disease diagnosis, CK-MB, an isoenzyme of creatine kinase (CK), was the marker of choice for AMI diagnosis. CK-MB is released in circulation 4-6 hours after symptoms of an AMI and usually peaks within 24 hours. Levels of CK-MB are back to normal range in 48-72 hours. The latter is different from the cardiac troponin pattern. Use of CK-MB in diagnosis of an AMI varies. Some institutions have discontinued assaying CK-MB in suspected AMIs; others use CK-MB measurements in conjunction with cTnI or cTnT. Because CK-MB returns to normal much faster than cardiac troponins, CK-MB measurements can be used when a reinfarction is suspected. In reinfarction, CK-MB concentration rises again after the return to baseline levels. Currently, CK-MB results do not predict future adverse cardiac events and do not have any prognostic or risk stratification use. | View Page |
| Diagnosis of an Acute Myocardial Infarction (AMI) An ESC/ACC consensus conference in 1999 defined cTnI and cTnT as the cornerstone biomarkers for diagnosis of AMI. If cardiac troponins are not available, then CK-MB should be used as a substitution marker. In 2007, the ESC/ACC/AHA published new criteria for an AMI:Elevated biomarkers and one of the following: Ischemic symptoms ECG changes indicating a new ischemic event Pathological ECG with Q waves (abnormal tracings found in AMI) Imaging evidence of new myocardial damage In 2002, ACC/AHA published practice guidelines for diagnosis of new category of heart disease, ACS. AACC and IFCC continue to improve guidelines in order to improve and clarify diagnosis. The goal is to increase detection of those presenting with an AMI (true positive) and decrease hospitalization of those who present with chest pain and have not experienced an AMI (false positive). | View Page |
| A 62-year-old male has been brought by ambulance to the emergency department. The patient is a smoker with a history of uncontrolled hypertension. While doing some outside painting at home, he became light-headed and complained of sharp pains in his chest. In the emergency department, an ECG and cardiac troponin I (cTnI) serial testing are ordered. Changes seen in the ECG pattern are consistent with an AMI.Baseline cTnI 0.03 ng/mL8 Hours cTnI 0.5 ng/mLCan this patient be diagnosed with an AMI according to the latest guidelines? | View Page |
| Cardiac Biomarkers and Congestive Heart Failure A patient with congestive heart failure (CHF) may exhibit signs and symptoms that are nonspecific; among these are edema, hypertension, shortness of breath, and weakness. Until recently the diagnosis of CHF was difficult, lengthy, and often concluded by ruling out other conditions. B-type natriuretic peptide (BNP) and/or the N-terminal fragment, NT-proBNP, are now routinely measured to diagnose CHF. ProBNP is the precursor of BNP. It is released from the left ventricle myocardium in response to mechanical stretch. This stretch is described as an increase in ventricular wall tension because of pressure and volume overload that occurs in CHF. ProBNP is then enzymatically cleaved to produce BNP and NT-ProBNP. BNP is the active hormone composed of 32 amino acids. The N-terminal fragment is a larger chain of 76 amino acids; this fragment is inactive. Studies indicate that NT-proBNP has the same clinical utility as BNP.Besides diagnosing CHF, the levels of BNP and NT-ProBNP correlate to the severity of the heart disease, assist in detection of CHF where patients are asymptomatic, and differentiate patients whose pulmonary disease presents with symptoms similar to CHF. | View Page |
| A 79-year-old diabetic and retired homemaker lives alone since the death of her husband 5 years ago. At age 75, she was diagnosed with an AMI and had another AMI last year. In the past 6 weeks, she has often been weak and often lacks energy. For the past 2 days, her symptoms have worsened and she is short of breath upon any exertion. Her daughter brings her to see the cardiologist who orders a BNP to evaluate her cardiac disease.BNP 520 pg/mL (Reference value = <100 pg/mL)What may this BNP result indicate when considered together with the patient's clinical symptoms? | View Page |
| The difference between the coagulation disorders Hemophilia A and Hemophilia B lies in: | View Page |
| Coagulation Disorders - Inherited Inherited disorders are those which are considered to be inborn, and have some familial linkage. Hemophilia A is a deficiency of coagulation factor VIII. It is the most commonly encountered hereditary based coagulation disorder. Found almost exclusively in males, its pattern of inheritance is sex-linked recessive. This disorder presents clinically with hemorrhagic events ranging in severity from mild to severe. Patients often present with spontaneous bleeding into their joints, a classic symptom of this affliction. The treatment of Hemophilia A often involves the administration of commercial factor VIII products. | View Page |
| Coagulation Disorders - Inherited Hemophilia B is a deficiency of coagulation factor IX. Found almost exclusively in males, its pattern of inheritance is sex-linked recessive. This disorder presents almost identically to Hemophilia A in terms of symptoms, and has a very similar pattern of inheritance. Be sure to keep in mind that while similar, Hemophilia A and B are caused by a deficiency in different coagulation factors. The treatment of Hemophilia B involves therapeutic administration of Factor IX concentrates. | View Page |
| Coagulation Disorders - Acquired Disseminated Intravascular Coagulation (DIC) is best described as a disorder of consumption, because clotting factors are depleted from the blood. Basically, clotting occurs randomly throughout the body, as opposed to just in the localized areas where vascular damage has occurred, consuming clotting factors and other components such as platelets in the process. Symptoms may range from a mild bleed, to severe, profuse bleeding, primarily dependant upon the availability of clotting factors. As more and more coagulation factors and components are consumed, the disorder progresses and symptoms worsen. Most heavily impacted are the levels of factors I, V, and VIII as well as the number of available platelets. Clinically, DIC is detected via an elevated (positive) FDP, positive D-dimer test, a prolonged PT and APTT, plus the manifestation of hemorrhagic episodes. DIC is diagnosed as two primary types, acute and chronic. Acute DIC manifests in a few hours or a few days, has a high mortality rate, and is seen in infections, obstetric complications, liver disease, and tissue injury. Chronic DIC is a secondary condition to some other disease state. Once you treat the primary disease, this type of DIC will go away. Treatment is often factor replacement therapy through the use of fresh frozen plasma and/or cryoprecipitate. | View Page |
| Introduction Hereditary hemochromatosis (HH) is a disorder of iron regulation that results in excessive dietary iron absorption through the gastrointestinal tract. Over time, the resultant iron overload and its deposition in tissue may lead to widespread organ damage, a variety of chronic disorders, and even death. Although it is a genetic disorder, clinical symptoms most typically become apparent in middle aged adults. Iron overload occurs in a variety of hereditary and acquired forms, known as iron storage diseases. HH is the most common cause of inherited iron overload. (1) Due to lack of awareness, HH often goes undetected or unrecognized by health care providers. Early detection to prevent the serious complications associated with iron overload has important consequences for reducing morbidity and mortality. Laboratory tests that assess iron levels and molecular assays for genetic mutatations are essential for both its detection and diagnosis. | View Page |
| Development of Iron Overload The amount of time needed for iron to increase to levels causing organ damage is variable and may be partially dependent on gender, dietary or other environmental factors, and unknown genetic factors. Blood loss through menstruation and pregnancy are thought to delay the onset of iron overload, and therefore symptoms of HH, in women. Similarly, regular blood donation may confer some degree of protection. The loss of hemoglobin within intact erythrocytes reduces the amount of iron available for recycling.As levels of storage iron increase, clinical features of iron overload, including hepatic dysfunction or failure, diabetes, hypogonadism, arthritis, cardiomyopathy, hyperpigmentation, and fatigue, may become evident.Symptomatic patients typically present in middle age between the ages of 30 and 60, although this is quite variable. Persons as young as 20 may show clinical signs and symptoms of HH.(6) In the US, males are more than twice as likely as females to be diagnosed with HH, and the majority of cases are found in Caucasians. | View Page |
| General Clinical Considerations Hereditary hemochromatosis (HH) is frequently discovered only during management of associated illness or routine health evaluations. It has been estimated that only a small percentage of all affected persons are actually diagnosed. Individuals with HH may be symptomatic for several years prior to diagnosis and may have consulted multiple health care providers.Under-diagnosis of HH is thought to occur due to:• Lack of specificity of early signs and symptoms• Asymptomatic status of some patients until damage to organs and tissues has occurred• Confusion with liver disease due to other causes• Insufficient awareness and knowledge of HHEarly identification of persons with HH is essential to prevent serious and irreversible complications associated with severe iron overload. A classic triad of skin hyperpigmentation (bronzing), type 2 diabetes, and hepatic cirrhosis has long been recognized as evidence of advanced iron overload. However, persons with HH may present with a much wider variety of signs and symptoms, particularly if they are seen before significant iron accumulation has occurred. Age of presentation and disease severity are highly variable. A diagnosis of HH is based on laboratory evidence of iron overload, genetic mutations associated with HH, and presence of clinical signs and symptoms consistent with HH.(10) | View Page |
| Which of the following does NOT contribute to the under-diagnosis of hereditary hemochromatosis (HH)? | View Page |
| Signs and Symptoms of HH Early signs and symptoms of hereditary hemochromatosis (HH) are vague, nonspecific, and variable. As iron overload progresses (late HH), signs and symptoms become more severe and are related to damage of specific organs. | View Page |
| Which of the following characterizes the early signs and symptoms of hereditary hemochromatosis (HH)? | View Page |
| Secondary Disorders of Iron Overload In addition to hereditary hemochromatosis (HH), there are other conditions of iron overload that must be considered in a differential diagnosis. Disorders such as sickle cell disease, thalassemia, sideroblastic anemia, congenital dyserythropoietic anemia, and liver disease may also cause iron overload. Transfusion-dependant patients and persons who abuse iron-containing vitamin supplements are also at risk. These conditions are usually described as secondary iron overload, in contrast to the primary iron overload of HH.Patient history, clinical signs and symptoms, biochemical and hematologic laboratory analyses, and possibly results of a liver biopsy may be needed to establish a diagnosis of a condition causing secondary iron overload. DNA tests for common HFE mutations are very likely the most important diagnostic tool for identifying HH as the cause of iron overload. In some patients, both secondary causes and HH may be contributing to iron overload. Differentiating the secondary causes of iron overload from HH is heavily dependent on the results of laboratory assays, but a complete discussion is beyond the scope of this course. | View Page |
| Diagnosing HH The diagnosis of hereditary hemochromatosis (HH) is made through a combination of laboratory tests and medical evaluation of a patient's signs and symptoms. Iron overload is identified by tests that evaluate iron metabolism, while molecular assays are needed to document mutations in the HFE gene or others such as hepcidin, hemojuvelin, or transferrin receptor. Individuals with documented iron overload who exhibit signs and symptoms consistent with HH and who possess HFE or other mutations are considered to have HH. Other causes of secondary iron overload may need to be ruled out.An example of a testing algorithm is shown. | View Page |
| Which of the following is (are) needed for a diagnosis of hereditary hemochromatosis (HH)? | View Page |
| What is the major determinant of prognosis for patients with hereditary hemochromatosis (HH)? | View Page |
| Molecular Tests DNA tests for HFE mutations associated with hereditary hemochromatosis (HH) are available in some clinical laboratories and reference laboratories. Testing for the presence of the C282Y is essential, although most labs also test for H63D and S65C mutations. Molecular testing is most appropriate for confirmatory testing of symptomatic individuals with altered iron studies (increased TS and SF), in pre-symptomatic individuals (increased TS, normal SF and liver function tests), and in family members of individuals diagnosed with HH. The use of genetic tests alone for routine screening of asymptomatic persons is not recommended for several reasons. A positive test indicating the presence of HFE mutations does not guarantee that an individual will develop clinically significant iron overload or predict severity of symptoms. A negative result (no HFE mutations present) does not rule out a diagnosis of iron overload because of genetic heterogeneity. Compared to biochemical analyses for iron, molecular assays are expensive. Finally, molecular testing may result in the diagnosis of a genetic disease, thus opening up the possibility for discrimination in health insurance coverage. Using molecular methods, DNA is extracted from leukocytes in whole blood samples or from buccal cells and analyzed for specific HFE mutations using polymerase chain reaction (PCR) with melt curve analysis. Currently there are no FDA-cleared products for HFE testing, and testing laboratories are using "home brew" reagents. This situation is expected to change as manufacturers submit products for FDA approval. | View Page |
| Initial Treatment Phlebotomy is considered the treatment of choice for patients with iron overload due to hereditary hemochromatosis (HH). Each unit of blood contains approximately 200 to 250 mg of iron. As erythrocytes are removed by phlebotomy, iron stores are mobilized and utilized in the production of new, circulating erythrocytes. Through periodic phlebotomies, stored iron is removed until iron-deficient erythropoiesis is induced. The initial, or iron reduction, phase of treatment typically consists of removing one unit (450 mL) of whole blood once or twice weekly. Prior to beginning phlebotomy, the patient’s hemoglobin and hematocrit must be checked to ensure that the patient is not anemic. A sample for serum ferritin is also collected at this time.Initial treatment goals include inducing iron deficient hematopoiesis without the development of debilitating symptoms of anemia. A hemoglobin concentration of 10.0 to 12.0 g/dL is often used as a target range. The initial treatment phase continues until excess stored iron is removed and ferritin levels decrease to approximately 50 ng/mL. (13) Ferritin and hemoglobin levels are periodically monitored during this phase. The number of phlebotomies needed to reduce iron levels and induce anemia is related to the degree of initial iron overload. Patients may be referred to a hematologist or gastroenterologist during the initial treatment phase. Many patients receive therapeutic phlebotomy services in a hospital or doctor’s office, but patients may also undergo phlebotomy at a blood center. Blood collected from persons with HH may be used for transfusion or as blood products if it has been collected from a facility with an approved variance from the US Food and Drug Administration. Not all blood centers have applied for or been granted this variance.(14)The initial treatment phase continues until excess stored iron is removed and ferritin levels decrease to approximately 50 ng/mL. Removal of excess stored iron may take from one month to three years. | View Page |
| Rationale for Treatment Treatment for hereditary hemochromatosis (HH) is typically indicated for iron overload in symptomatic patients. The goal of therapy is to reduce stored iron which may result in reversal or resolution of some symptoms and improve prognosis. Causes of death in patients with HH include serious medical conditions such as hepatocellular carcinoma, cirrhosis, cardiomyopathy, and diabetes. Ideally, treatment should begin before these conditions develop. The earlier HH is detected, before the onset of severe organ damage, the lower the risk of mortality. | View Page |
| The general signs and symptoms of smallpox include: | View Page |
| The early symptoms of anthrax include: | View Page |
| Agent: Smallpox (Virus) Most likely means of dissemination: As an aerosolPrimary route of entry: InhalationGeneral signs and symptoms: High fever, extreme lethargy, severe headache, severe backache, severe abdominal pain, with a rash that starts as red bumps but quickly develops into small, itchy blisters. Photo courtesy of the CDC archives. | View Page |
| Agent: Anthrax (Bacterium) Most likely means of dissemination: In a solid state Primary route of entry: Inhalation (also ingestion and absorption) General signs and symptoms: Early symptoms are flu-like—chills, fever, nausea, and swelling of lymph nodes. | View Page |
| Agent: Pneumonic plague (Bacterium) Most likely means of dissemination: AerosolPrimary route of entry: InhalationGeneral signs and symptoms: High fever, chills, headache, coughing up of blood (hemoptysis), and toxemia, progressing rapidly to difficulty in breathing (dyspnea), and bluish discoloration of the skin and mucous membranes (cyanosis).There is another form of the disease called “bubonic plague”. While it is caused by the same organism, it is not transmissible through human contact. Pneumonic plague is transmissible through human contact. | View Page |
| Agent: Botulism (bacterium) Most likely means of dissemination: Aerosol (eating contaminated food)Primary route of entry: Inhalation (oral)General signs and symptoms: Difficulty with speaking, swallowing, or blurred or double vision, drooping eyelids (ptosis), dilated pupils, dry mouth, decreased gag reflex, weakening of the reflexes (hyporeflexia), abnormal sensations such as numbness, prickling, tingling, and arm or leg weakness.Botulism is caused by a neurotoxin and technically could be classified as a chemical WMD. For our discussion it is placed under biological agents because the toxin is derived from a bacterium. Botulism is potentially life-threatening, producing a characteristic clinical picture of muscular paralysis leading to respiratory failure. Photo courtesy of the CDC archives. | View Page |
| Agent: Tularemia (bacterium) Most likely means of dissemination: Solid or aerosolPrimary route of entry: Inhalation, absorption, or ingestionGeneral signs and symptoms: Sudden fever, chills, headaches, muscle aches, joint pain, dry cough, progressive weakness, and pneumonia.The disease is not transmissible through human contact. When used as a WMD, infection would be acquired by handling infected material, eating or drinking contaminated food or water or by breathing in the bacterium. | View Page |
| Agent: Viral hemorrhagic fevers (Ebola, Marburg, Lassa and Argentine) Most likely means of dissemination: Solid, liquid or aerosolPrimary route of entry: Absorption, inhalation, ingestionGeneral signs and symptoms: Vary by type of viral hemorrhagic fever (VHF), but initial signs and symptoms often include marked fever, fatigue, dizziness, muscle aches, loss of strength, and exhaustion. Severe cases of VHF often show signs of bleeding under the skin, in internal organs, or from body orifices like the mouth, eyes, or ears. Photo courtesy of the CDC archives. | View Page |
| Early symptoms of inhaled Anthrax include | View Page |
| Blood Agents Example: Hydrogen cyanidePhysical Properties: Highly volatile gas with a bitter almond odor.General Signs and Symptoms: Violent convulsions, stoppage of breathing, cardiac failure.Relative Rate of Action: Incapacitation within minutes and death within 15 minutes. | View Page |
| Lung-damaging or Choking Agents Example: Phosgene Physical Properties: Heavy gas, smells like fresh cut hay. General Signs and Symptoms: Coughing and choking, followed by tightness in chest, nausea, vomiting and headache. Death is due to the accumulation of fluid in the lungs. Relative Rate of Action: Immediate in high concentrations to several hours in low concentrations. | View Page |
| Blister Agents Example: MustardPhysical Properties: Oily liquid that may or may not have a garlic odor.General Signs and Symptoms: Initial redness of skin followed by blister formation, irritation to eyes, hoarseness or hacking cough, possibly nausea and vomiting.Relative Rate of Action: Usually 4 to 6 hours before onset. Photo courtesy of the Wikimedia Commons. | View Page |
| Nerve Agents Examples: Tabun, SarinPhysical Properties: Colorless liquid, usually odorless, but may have a fruity smell.General Signs and Symptoms: Difficulty in breathing, contraction of the pupils, blurred vision, headache, nausea, convulsions, and eventually death.Relative Rate of Action: Rapid, within minutes. Photo courtesy of the Wikimedia Commons. | View Page |
| In Case of a Biological Attack Listen to the radio for instructions from authorities on whether to evacuate or stay put. If told to stay inside, seek shelter in an internal room or a room with as few doors and windows as possible. Turn off all ventilation and as best as possible seal all openings in windows and doors. Continue to monitor the radio. Some biological attacks may be more immediately apparent than others. Monitor your radio, television, or medical alert for instructions from authorities regarding disease symptoms and how and where to seek medical attention. If you do come in contact with a visible, potentially infectious substance, you should remove and bag your clothes and personal items, wash yourself with warm soapy water immediately, and seek medical assistance. | View Page |
| Repetitive Motion Injuries Repetitive motions can cause a variety of disorders that affect nerves, tendons, and muscles. Symptoms can include tingling or numbness in the fingers or hands, decreased range of motion, decreased grip strength, sleep interupted by numbness or discomfort in the hands, pain in fingers, hands, or wrist, or pain shooting up into the forearms or arms.Some common afflictions that could affect laboratory workers due to the nature of their jobs are listed in the table below. Condition Symptoms Cause Carpal tunnel syndrome Pain that radiates up the arm, numbness or tingling in the thumb, index, or middle finger and weakness in the wrist and hand Compression of the median nerve that runs from the forearm into the hand Thoracic outlet syndrome Numbness and tingling in the hand, intensified with overhead activities Compression of the nerves and blood vessels between the neck and shoulder Radial tunnel syndrome Elbow pain, pain near the base of thumb, or pain anywhere in between. A common symptom is wrist weakness. Compression or entrapment of the radial nerve; may be caused by repetitive wrist and finger extension or repetitive forearm turning. Tendinitis Stiffness, tightness, and burning sensation; may experience a deep nonspecific pain. Grip impairment. Occurs most often in the tendons of the fingers, thumb, forearm, elbow, and shoulder. Repetitive motions or maintaining an awkward position that stresses tendons beyond their strength. Friction from overuse can cause inflammation. Tenosynovitis Pain, swelling, difficulty moving the joint in the affected area Inflammation of the tendon sheath | View Page |
| Eyestrain Eyestrain is a common problem associated with the prolonged use of computers or microscopes. Symptoms of eyestrain include: Blurred or double vision Itchy, dry, sore, burning, or tired eyes Headaches Color fringes / after images Sensitivity to light | View Page |
| Which of the following is a symptom of a repetitive motion injury? | View Page |
| Light sensitivity and headaches are symptoms of what disorder? | View Page |
| A 20 year-old female was admitted into the hospital complaining of 10 to 15 bloody mucous stools per day, fever, gastrointestinal disturbances, abdominal pain, and nausea. The preliminary O & P report went out as "Probable Entamoeba histolytica trophozoites and cysts, confirmation pending." This patient is most likely suffering from: | View Page |
| Match each organism with its respective associated condition: | View Page |
| A 32 year old male was seen in the emergency room with gastrointestinal discomfort. Upon questioning the patient it was learned that he first began feeling ill after spending a day at the park where he swam and played volleyball barefooted. He first noticed a lesion on his foot. Later, he developed vague respiratory symptoms. Now his largest complaint is severe abdominal pain along with occasional vomiting. This patient is most likely suffering from: | View Page |
| This stool parasite measures 55 µm by 50 µm and is the causative agent of: | View Page |
| This parasite, found in striated muscle, is responsible for which of the following conditions? | View Page |
| Which of the following symptoms are associated with an infection of the parasite pictured below? | View Page |
| Perianal itching is the major symptom of infection with both forms of the organism pictured here. This parasite is the causative agent of: | View Page |
| Arrange the following hookworm symptoms in order of their occurance based on the parasite's migration through the body beginning with human transmission: | View Page |
| A 68-year-old female, who recently vacationed in Brazil, presented to her physician exhibiting overall weakness, fever, and enlarged lymph nodes. Blood was collected for culture and parasitic examination. The culture was negative. This suspicious form was recovered upon examining the Giemsa-stained preparation. This patient is most likely suffering from: | View Page |
| Match each parasite named below with its respective primary symptom: | View Page |
| Label the morphologic structures on this parasite form: | View Page |
| A 21 year old male presented in the emergency room with symptoms resembling a liver infection. The patient complained of abdominal pain, fever, cough, nausea, vomiting and constipation alternating with diarrhea. Further examination revealed the presence of a hepatic abscess. This suspicious form was recovered following parasitic examination of a sample from the abscess and measures 20 µm. What condition is the patient most likely suffering from? | View Page |
| A 55 year old female, who recently returned from an extensive trip to China, presented to her physician complaining of diarrhea and abdominal cramps. The doctor ordered a complete blood count (CBC), chem 21 panel, and stool for culture and parasite examination (O & P). The CBC revealed pronounced eosinophilia. The chem 21 and stool culture were unremarkable. The O & P revealed suspicious forms like the one below that each measured approximately 140 µm by 80 µm. This patient is most likely infected with: | View Page |
| A 27 year old male was seen in the emergency room complaining of diarrhea. He had no other symptoms and was in very good health. The doctor ordered a stool for culture and parasite study. The culture revealed no enteric pathogens. This suspicious form was seen on the wet preparations and the permanent stain. It measured 16 µm. With which of the following parasites is this patient most likely infected? | View Page |
| A 31 year old male missionary worker recently returned from Africa where he helped a small rural community update their sanitation practices. He presented to his physician weak and complained of recent weight loss, abdominal pain, and diarrhea that was often bloody. The doctor ordered a battery of tests including a complete blood count (CBC) and stool for parasite examination. The CBC revealed eosinophilia and anemia. This suspicious form was seen on the wet preparations. It measured 52 µm by 27 µm. What parasite is mostly likely present? | View Page |
| A 4 year old female from South Carolina was rushed to the emergency room who was suffering from malaise, bloody diarrhea and abdominal pain. Examination revealed rectal prolapse. Stool was submitted for parasitic examination and this suspicious form was seen. It measures 45 µm by 20 µm. Which of the following is the correct identity of this suspicious form? | View Page |
| What term is defined as the presence of arthropods in or upon a human host: | View Page |
| An 8 year old girl is protected from severe hemolytic anemia by an elevated fetal hemoglobin level ( hemoglobin F). | View Page |
| A 5-year-old girl was brought to a physician's office because of fever and viral-type illness symptoms. Her blood pressure was elevated.Hemogram: hemoglobin 9.1g/dL (normal 12.0 - 16.0 g/dL), hematocrit 28% (normal 37 - 48%), MCV 80 fl (normal 86 - 98 fl), RDW 13.1% (normal 11 - 15%), platelets 90.1 X 109/L (normal 150 - 450 X 109/L) WBC 9.6x109/L (normal 4.3 - 10.8 x 109/L).The peripheral blood smear is represented in the photograph.Which of the following are the most likely associated conditions? | View Page |
| Considering the predominance of microspherocytes on the blood smear, and the patient's jaundiced condition, what is the most likely diagnosis? | View Page |
| Atypical smear: Case follow-up The patient whose blood smear is shown in the photograph was a 32-year-old female from Virginia who came to the high country of Colorado to ski. The day after arrival, she experienced shortness of breath, fatigue, and upper abdominal pain. She was seen in a medical center in the mountains where a working diagnosis of altitude sickness was made. A CBC revealed RBCs 5.1 x 1012/L, hemoglobin 12.8g/dL, MCV 60fL, hematocrit 40.9%, and normal total WBC, differential, and platelet count. The RDW was normal. Further questioning revealed a previous diagnosis of heterozygous beta-chain thalassemia. No other abnormal hemoglobins were found on hemoglobin electrophoresis, but HbA-2 was elevated to 5%, supporting the diagnosis of beta thalassemia. The patient's poikylocytosis and anisocytosis may be a clue to an underlying erythrocyte abnormality. Persons with iron deficiency anemia may experience various degrees of hypoxia upon arriving at high altitudes. Those with sickle cell disease and thalassemia minor (as in this case) may experience bone pain or other symptoms of "crisis" and/or alteration in the appearance of their erythrocytes upon sudden high altitude exposure. The classic teaching is that in differentiating iron deficiency anemia from thalassemia, increased RDW would favor iron deficiency; normal RDW favors thalassemia. | View Page |
| Literature and online resources Literature Dutton RP, Shih D, Edelman BB, Hess J, Scalea TM. Safety of uncrossmatched type-O red cells for resuscitation from hemorrhagic shock. J Trauma. 2005 Dec;59(6):1445-9. Johnson ST, Rudmann SV,Wilson, SM. Serologic problem solving strategies:a systematic approach. Bethesda, MD: AABB, 1996.Online resourcesThe following are online examples of good practice. The information should not be used as a substitute for technical and clinical judgment. Medical and technical information becomes obsolete quickly and current sources relevant to the user's location should always be consulted. Urgent requirements for blood (Calgary Laboratory Services, Calgary,Alberta, Canada) Online resource for laboratory's clients Why is there never enough O Rh negative blood? (American Red Cross) Advice for physicians on how to help prevent shortages of O Rh negative blood Transfusion reactions: Transfusion complications (Canadian Blood Services) Education website for CBS's hospital customers REACT (Sunnybrook HSC, Toronto, ON, Canada) Pocket reference card for nurses on signs and symptoms of transfusion reactions Quick cals (online calculator of p values for Fisher's exact test) Use a one-tailed test (since we would expect an antibody to react with red cells that are positive for the corresponding antigen) | View Page |
| Follow-up with clinical staff The patient's physician was notified that compatible blood was unavailable and that the patient's antibody was still being investigated.When asked whether or not the patient was experiencing a transfusion reaction due to the transfusion of the two unmatched and incompatible O Rh negative RBC, the nurse in the OR stated that the patient was undergoing surgery and completely sedated. A transfusion reaction was not apparent but they would investigate and closely monitor.Hemolytic Transfusion Reactions (HTR)Before proceeding to the next page, make a short list of signs and symptoms associated with immediate hemolytic transfusions reaction and another list associated with delayed hemolytic transfusion reactions. | View Page |
| Immediate HTR - Signs and symptoms The following signs and symptoms are associated with acute HTR due to ABO incompatibility but can be associated with other blood group incompatibilities. ABO incompatibility typically results from patient misidentification.The more serious symptoms result from intravascular hemolysis (IVH) caused by antibodies such as anti-A and anti-B that can bind complement to C9.Signs and symptoms typically appear within minutes of the transfusion but can occur anytime during the transfusion. They may include: 1. Burning sensation along the vein being transfused (IVH due to complement activation to C9)*2. Lower back pain in the area of the kidneys (renal failure with subsequent oliguria/anuria) *3. Unexplained bleeding/oozing from a surgical site (fibrinolysis following DIC)*4. Hypotension leading to hypovolemic shock (release of vasoactive substances caused by C3a and C5a)5. Tightness in substernal area of the chest (bronchial constriction due to release of vasoactive substances caused by C3a and C5a fragments)6. Other symptoms: fever, chills, skin flushing, dyspnea, wheezing, anxiety, malaise, nausea, headache. * If untreated, these complications may lead to patient death. | View Page |
| Delayed HTR - Signs and symptoms Delayed HTR often go undetected as the symptoms are usually mild and subclinical (death has occurred, but rarely). Symptoms may not occur until days after transfusion when the patient has left the hospital. Donor red cell destruction is usually by extravascular hemolysis (EVH). Signs and symptoms can include: Fever with or without chills Unexplained drop in hemoglobin and hematocrit Transient jaundice due to elevated serum bilirubin | View Page |
| Signs and symptoms - Job Aids Some blood safety standards require that a list of common signs and symptoms of suspected adverse reactions be included in both nursing and transfusion service manuals. Several organizations have developed job aids to help clinical staff recognize the signs and symptoms of various suspected transfusion reactions and to suggest appropriate actions (e.g., see REACT in Online Resources). | View Page |
| Signs and symptoms - Precaution Signs and symptoms are used only as a general guide to the type of transfusion reaction that may be occurring.Lower back pain, for example, would suggest an acute hemolytic reaction, whereas fever is associated with several types of reactions: Hemolytic (immediate and delayed) Febrile Bacteriogenic | View Page |
| Which of the following signs and symptoms is most likely to indicate a severe immediate hemolytic transfusion reaction? | View Page |
| Epidemiology of the Virus The Influenza A 2009 H1N1 virus spreads from person to person in a similar way to the seasonal flu in previous years.The primary route of influenza virus transmission and infection are by respiratory droplets and aerosols. Transmission may also occur via contaminated hands (person-to-person) and surfaces. Infected individuals can shed the virus and spread Influenza A 2009 H1N1 to others anywhere from 1 day prior to getting sick up until 5-7 days after symptoms arise. This range of viral shedding can be even longer in children and in some individuals who are immunocompromised. | View Page |
| How 2009 H1N1 Differs from Seasonal Flu Viruses The 2009 Influenza A H1N1 virus is both similar and different from previous influenza A viruses that have caused seasonal flu in recent years. The symptoms associated with the H1N1 virus are very similar to those of other influenza A viruses causing seasonal flu. One difference between the influenza A 2009 H1N1 virus and seasonal influenza A viruses is the time of year in which the infection is at its peak. The influenza 2009 H1N1 virus was prevalent during warmer weather months in 2009, whereas the peak time for seasonal influenza viruses is winter months.Another way in which the H1N1 virus differs from seasonal flu viruses is the age group that is most affected. The number of cases and severity of the disease has been greater in the younger population, whereas most seasonal influenza virus-related deaths have been reported in those age 65 and older.• | View Page |
| Signs and Symptoms of the H1N1 Virus Symptoms of the Influenza A 2009 H1N1 virus are similar to what is currently recognized as typical flu-related symptoms. The most common symptoms for the H1N1 virus include: fever (greater than 100.0º F or 37.8 º C) sore throat fatigue cough runny / stuffy nose chills diarrhea nausea / vomiting headaches body aches (muscle & joint pain) More severe symptoms may be present. | View Page |
| How Severe is the Illness? •Influenza A 2009 H1N1 virus-related symptoms range from mild to severe. Many infected individuals are able to recover without medical treatment. Occasionally, some individuals require hospitalization, and these patients receive supportive care and antiviral treatment. Serious infections from the 2009 H1N1 virus have resulted in some patient fatalities, usually due to secondary bacterial pneumonia or other respiratory complications.It is important to note that approximately 70% of the individuals that require hospitalization due to H1N1 infection, have also had one or more previously recognized underlying medical condition that may compromise an effective immune response. These conditions include, but are not limited to: diabetes heart disease asthma kidney disease neurocognitive diseases pregnancy | View Page |
| Which of the following is NOT a typical symptom associated with the 2009 H1N1 virus? | View Page |
| Guidelines for Diagnostic Testing and Treatment According to the CDC guidelines, patients with clinical illness consistent with uncomplicated influenza who reside in an area where influenza viruses are circulating may not require diagnostic influenza testing for clinical management. Most mild cases of H1N1 infection are self-limiting and do not require confirmation. However, if a patient is hospitalized due to the severity of the symptoms, or if the diagnosis of the patient will provide needed information to the physician to direct clinical care, infection control decisions, or management of close contacts, diagnostic influenza testing should be done. In any case, if a decision to use antiviral treatment is made, the treatment should commence as soon as possible, without waiting for the results of confirmatory diagnostic tests. | View Page |
| Laboratory Tests A variety of tests are available for the detection of influenza A viruses, including the 2009 H1N1 strain. These tests include: rapid antigen tests, direct fluorescent antibody tests to detect the presence of virus in patient specimens, shell vial cell cultures, classical tube cell cultures, and reverse transcriptase PCR (RT-PCR), which detects influenza-specific viral genes. These tests differ in sensitivity, specificity, availability, and the ability to distinguish between different influenza strains and subtypes, such as influenza A 2009 H1N1.The rapid tests, such as the direct rapid antigen tests or immunofluorescence assays, have lower sensitivity and specificity compared to cell culture and the RT-PCR based tests. Rapid tests vary in their ability to detect the 2009 H1N1 virus. The range of sensitivity is 10% to 70% and none of the rapid tests that are currently available are specific for H1N1. However, results of rapid tests are available within 30 minutes to one hour so that a positive test will provide further information toward a diagnosis when it is coupled with a patient's symptoms. A few FDA-cleared RT-PCR kits are available for the detection of influenza A viruses. For the subtyping of influenza A viruses, such as Influenza A seasonal H3N2, and 2009 H1N1, the FDA has given the status of "Emergency Use Authorization" (EUA) to a few of the RT-PCR kits; currently available kits under this emergency status category include those made by the CDC, ELITech, Prodesse, Focus Diagnostics, and Roche. (http://www.fda.gov/MedicalDevices/Safety/EmergencySituations/ucm161496.htm)State Departments of Health have been provided with RT-PCR kits from the CDC for the subtyping of influenza A viruses. This testing has also been FDA-reviewed and given the status of EUA. State and local health department guidelines determine which specimens should be submitted to public health laboratories for RT-PCR testing. In addition, several commercial reference laboratories, academic labs, and hospital labs have been able to perform influenza A subtyping for 2009 H1N1 under the same EUA status. Any laboratory that performs an EUA method would be required to perform an internal validation process. | View Page |
| Specimen Collection and Storage The manufacturer’s instructions (package insert) lists the acceptable respiratory specimen types for testing in each rapid influenza A/B test kit. The following specimen types are preferred for influenza virus diagnostic testing: nasopharyngeal swabs, washes and aspirates; endotracheal aspirates, and bronchoalveolar lavage (BAL). The CDC recommends nasopharyngeal washes for patients less than 3 years old and nasopharyngeal swabs for patients over 3 years of age. The image on the right illustrates the correct area to swab when collecting a nasopharyngeal specimen. Two swabs or washes would facilitate both rapid influenza A/B testing and a second specimen that could be sent for confirmatory H1Ni testing by RT-PCR if needed. Nylon fiber flocked swabs have been shown to be more effective than dacron or other woven fiber swabs for the collection of virus from the nasopharynx. The soft brush-like nylon fiber swabs are more efficient at collecting cells and viral particles and subsequently releasing virus when swabs are placed into viral transport media due to the capillary action of the flocked swab. It is suggested that the ill patient should have specimens collected as soon as possible after the onset of symptoms. For certain patients, more than one specimen may be necessary to confirm the presence of the virus. Nasopharyngeal swabs should be placed into sterile universal transport medium (UTM) or comparable viral transport media and promptly delivered to the laboratory within 2 hours. If processing is delayed longer than 2 hours, respiratory specimens should be placed in a refrigerator (held at 40C). Viruses usually remain stable for 2 to 3 days when held at this temperature. | View Page |
| Tuberculosis infection The natural history of TB infection is usually followed by an immune response and latency after exposure. In about 5-10% of cases, the latent period progresses to an active infection.The organism that causes TB infection is Mycobacterium tuberculosis. This organism is pictured in the photograph to the right as observed when stained with acridine orange stain. Infection occurs when a susceptible person inhales droplet nuclei containing Mycobacterium tuberculosis and the organism reaches the alveoli of the lungs.About 2-12 weeks after infection, the immune system limits multiplication of additional bacteria and the immunological test becomes positive.Latent tuberculosis infection (LTBI) is the stage when the viable organism remains in the body, and the patient has no symptoms and is non-infectious.Most infected persons do not experience clinical illness and are noninfectious. About 5-10% of persons infected with Mycobacterium tuberculosis who are not treated will develop TB during their lifetime. The risk for progression is highest during the first several years after infection.TB infects the lungs most often; however, it can infect almost any organ in the body, including bones and joints. | View Page |
| Symptoms Symptoms of active TB include:coughing for more than 3 weeks,loss of appetite,unexplained weight loss,night sweats,bloody sputum,hoarseness,fever,fatigue,and chest pain.
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| A Word of Caution Symptoms of TB can mimic other diseases and the physician must consider the patient's history as well as physical symptoms before making a final diagnosis. | View Page |
| Health Care Worker Tuberculosis Screening All HCWS receive baseline TB screening upon hire, using either the two step skin test or BAMT. Annual screening varies depending on setting risk. In low risk settings, screening is not necessary unless an exposure occurs. In a medium risk setting, all HCWS are screened for symptoms and HCWs with negative baseline results are tested.In a potential ongoing transmission setting, HCWs receive testing every 8-10 weeks until lapses are corrected. | View Page |
| Match the recommended frequency for TB screening of a healthcare worker with the risk category of the healthcare setting from the drop-down box: | View Page |
| Protect Yourself Healthcare workers must be alert for signs and symptoms of TB to protect themselves from inadvertent exposure.Help protect yourself, coworkers, patients, and visitors by: Having current TB screening according to the risk classification of your setting, Understanding the risks of TB in your work area, Practicing good infection control at work and at home. | View Page |
| A peripheral blood smear is submitted for morphology review. The patient is a 10 year-old boy with symptoms suggesting appendicitis and an appendectomy is being considered. The total WBC is 18.5 X 1000/uL, RBC's = 5.45 X 1M/uL, hemoglobin = 16.0 g/dL, hematocrit 48.2%;wbc differential: Segs = 53%, bands = 42% (two of which are shown in the photograph), monocytes = 2%, and lymphocytes= 2%. These findings support the diagnosis of appendicitis. | View Page |
| Case Follow-up Illustrated in the upper and lower photographs are two-lobed, eye glass ("pince nez") nuclei of neutrophils typical for patients with Pelger-Huet anomaly. In addition to the characteristic two lobes connected by a delicate bridge, the dense, homogeneous nuclear chromatin helps to define Pelger-Huet anomaly. Since the peripheral blood smear did not support the diagnosis of appendicitis in this patient, and since abdominal pain localized to the right lower quadrant never developed, the boy was hydrated with intravenous fluid and observed. After hydration, his constitutional symptoms improved and the abdominal pain subsided. In fact, the lad was back on the ski slopes the next afternoon. People entering high altitude where the humidity may be very low are susceptible to dehydration and may experience symptoms related to mountain sickness. Therefore, close observation and hydration may be the best practice in monitoring patients with stories and findings similar to this one. A further lesson here is that technologists must be alert to the possibility of Pelger-Huet anomaly if a high white blood cell count with a high percentage of band neutrophils with strikingly uniform morphology and without toxic granulation are found. Inappropriate therapy or an invasive procedure as was contemplated here may be avoided by a proper smear assessment and clinical corroboration. | View Page |
| Case history A 14 year-old boy came to the physician's office with a sore throat that progressively worsened over a three day period. His posterior pharynx was swollen ,shiney and erythematous. The boy complained of pain on swallowing. His temperature was 98.5F. A rapid direct streptococcal antigen test was positive. However, his symptoms did not subside over the next two days while on antibiotic therapy. Anorexia and nausea were persistent and compounded by a frontal headache. Cervical lymph nodes became noticeably enlarged. The results of the CBC were: WBC 11.9/mm3 with 17% segmented neutrophils, 5% bands, 72%(60% atypical--see photograph)lymphocytes and 6%monocytes. All red cell findings were normal. A monospot test was positive. This is a case of group-A streptococcal infection superimposed on infectious mononucleosis. Symptoms subsided in 3 weeks following completion of the antibiotic therapy. | View Page |