Blog http://www.clinlabnavigator.com/Clinlab/Blog/ Fri, 18 Aug 2017 21:15:28 -0400 Joomla! - Open Source Content Management en-gb Tickborne Infectious Disease Review http://www.clinlabnavigator.com/tickborne-infectious-disease-review.html http://www.clinlabnavigator.com/tickborne-infectious-disease-review.html

Tickborne diseases are increasing in the United States, and the geographic range of tick vectors is expanding. Tickborne diseases are challenging to diagnose, because they present with vague symptoms such as fever, constitutional symptoms, and nonspecific laboratory abnormalities. A high degree of clinical suspicion is required to make a diagnosis, as patients often do not recall a tick bite.

Most tickborne infections occur between April and October when tick populations peak. Because we are in the middle of the tickborne illness season, I thought it might be helpful to provide a brief review of the most common tickborne diseases, including diagnostic laboratory testing.

Rickettsia rickettsia is an obligate intracellular gram-negative coccobacillus that is transmitted by the American dog tick and causes Rocky Mountain Spotted Fever (RMSF). RMSF can be transmitted after only 2 to 20 hours of tcik attachment. Symptoms begin with sudden onset of fever and headache 3 to 12 days after a tick bite. A rash occurs in 90% of RMSF cases, usually within 2 to 5 days after fever onset. Classically, the rash progress from macules to petechial on wrists, forearms & ankles, spreading centripetally to the trunk, palms and soles. Without appropriate therapy, death occurs 7 to 15 days after symptom onset. Laboratory tests may reveal thrombocytopenia and anemia. White blood cell count may be increased or decreased. Other laboratory findings include hyponatremia, elevated AST and CK enzymes, prolonged PT and aPTT and decreased fibrinogen. Diagnosis is by serologic testing for both IgM and IgG RMSF antibodies. Antibody response may not be detected in the first 7 to10 days after illness onset. Treatment should not be delayed because of an initially negative result. PCR testing for RMSF is not reliable since the organism is predominantly found in endothelial cells and not circulating in peripheral blood.

Tularemia is a zoonotic infection caused by the gram-negative bacterium Francisella tularensis. Tularemia has variable symptoms but usually manifests with fever, flu-like illness, and lymphadenopathy. Route of infection is likewise variable and may include tick bites, as well as cat bites and other animal exposures. Diagnosis can be made by testing for Francisella tularensis antibody or by culture of blood or infected tissues, such as wounds or lymph nodes. Clinicians should notify the microbiology laboratory at the time of culture submission when tularemia is the suspected diagnosis, so that appropriate bacterial media can be utilized and precautions can be taken to avoid laboratory exposure to the organism.

Ehrlichiosis and anaplasmosis are closely related diseases caused by small, obligate intracellular bacteria, similar to rickettsia. Ehrlichia chaffeensis and Anaplasma phagocytophilum are the causative agents of human monocytic ehrlichiosis and human granulocytic anaplasmosis, respectively. Transmission is through tick vectors Amblyomma americanum (Lone Star tick) or Ixodes scapularis (deer tick or blacklegged tick), which is also associated with Lyme disease. Incubation period between tick bite and disease onset is generally 5 to 21 days.

Symptoms of ehrlichiosis and anaplasmosis are nonspecific including fever, malaise, and headache. Secondary symptoms of anorexia, nausea, vomiting, diarrhea, and abdominal pain are more frequent in ehrlichiosis. Serious complications include hypotension, respiratory failure, meningoencephalitis, acute renal failure and coagulopathy. Laboratory findings include leukopenia, thrombocytopenia, and elevated hepatic transaminases. CSF often shows elevated protein and lymphocytosis.

Recommended testing for ehrlichiosis and anaplasmosis includes serology and PCR. Serology includes IgG and IgM antibody for both organisms. Since both IgM and IgG antibodies may be negative during the first 7 to 14 days of infection, PCR is recommended for suspected acute disease. Examination of peripheral blood smears for morulae has a sensitivity of 20% and is not recommended as a diagnostic test.  Blood cultures do not detect these bacteria.

Lyme disease, due to Borrelia burgdorferi, is the most common tick-transmitted disease in the United States. A B. burgdorferi carrying tick has to be attached for at least 36 hours in order for the bacteria to be efficiently transmitted to an individual. Following transmission, the incubation period is typically 7 to 14 days, but can range from 3 to 32 days. The first phase of infection is the appearance of a erythema migrans rash, which occurs in approximately 80% of individuals. Some patients may also experience fatigue, malaise, myalgia, headache, and lymphadenopathy. During the next few weeks, untreated individuals may develop neurologic disease including meningitis, cranial neuropathy, and motor or sensory radiculoneuropathy. Patients may develop Bell’s Palsy and a oligoarticular arthritis involving the large joints.

Available testing for Lyme disease includes Lyme total antibody, which reflexes to Western blot confirmation when positive, as well as Lyme PCR for suspected acute infections. A negative result does not exclude Lyme disease, especially if the sample was collected within 2 weeks of symptom onset. If Lyme disease is strongly suspected, a second specimen should be tested 4 to 6 weeks after the first. Early administration of antibiotics may weaken or delay the antibody response.

Babesiosis is a malaria-like illness caused by the intraerythrocytic protozoan Babesia microti. Babesiosis is usually a tickborne illness but can also be transmitted by blood transfusion and transplacental spread. Ixodes scapularis tick is the vector for Babesia microti. Transmission requires 24 to 72 hours of attachment to a host. Babesia species cause illness by lysing erythrocytes, with resultant cytokine release. Symptoms usually appear 1 to 4 weeks after transmission and are nonspecific. Physical findings may include splenomegaly, hepatomegaly, jaundice, petechiae and ecchymosis. Laboratory findings include thrombocytopenia, hemolytic anemia, elevated liver enzymes and prolonged coagulation tests.

The diagnosis of babesiosis is most commonly made by finding the intraerythrocytic ring form of the organism (trophozoite) on Giemsa or Wright-stained blood smears. PCR can detect Babesia infection with negative blood smears.

Powassan virus is a flavivirus carried by Ixodes scapularis ticks. The most common presentation is viral encephalitis. Rash and GI symptoms may also occur. Testing for POWV infection is not usually included in arbovirus encephalitis panels and must be requested specifically. Serum and cerebrospinal fluid can be tested for anti-POWV IgM by immunoassay. Positive results are confirmed with a POWV neutralization test or detection of IgG antibody.

Two new viruses, Heartland and Bourbon, have been discovered in Missouri and Kansas patients. These viruses are believed to be transmitted by tick bites. Symptoms may be nonspecific including fever, anorexia and diarrhea. Laboratory findings include leukopenia, thrombocytopenia & elevated liver transaminases. Testing for Heartland and Bourbon viruses is available only through the CDC. The appropriate state health department must be contacted with case specifics to obtain testing.

Some ticks transmit more than one type of infection and, therefore, coinfection with multiple pathogens is possible. Coinfection may increase he severity of disease.  For example, Ixodes scapularis tick can transmit the organisms responsible for Lyme disease, anaplasmosis, babesiosis and Powassan infection.

Reference

Eickhoff C and Blaylock Jason, Tickborne diseases other than Lyme in the United States. Cleveland Clinic J Med. July 2017;84:555 – 567.

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fvplapp@icloud.com (Fred Plapp) Blog Sun, 13 Aug 2017 20:54:19 -0400
Tickborne Infectious Diseases http://www.clinlabnavigator.com/tickborne-infectious-diseases.html http://www.clinlabnavigator.com/tickborne-infectious-diseases.html

Tickborne diseases are increasing in the United States, and the geographic range of tick vectors is expanding. Tickborne diseases are challenging to diagnose, because they present with vague symptoms such as fever, constitutional symptoms, and nonspecific laboratory abnormalities. A high degree of clinical suspicion is required to make a diagnosis, as patients often do not recall a tick bite.

Most tickborne infections occur between April and October when tick populations peak. Because we are in the middle of the tickborne illness season, I thought it might be helpful to provide a brief review of the most common tickborne diseases, including diagnostic laboratory testing.

Rickettsia rickettsia is an obligate intracellular gram-negative coccobacillus that is transmitted by the American dog tick and causes Rocky Mountain Spotted Fever (RMSF). RMSF can be transmitted after only 2 to 20 hours of tcik attachment. Symptoms begin with sudden onset of fever and headache 3 to 12 days after a tick bite. A rash occurs in 90% of RMSF cases, usually within 2 to 5 days after fever onset. Classically, the rash progress from macules to petechial on wrists, forearms & ankles, spreading centripetally to the trunk, palms and soles. Without appropriate therapy, death occurs 7 to 15 days after symptom onset. Laboratory tests may reveal thrombocytopenia and anemia. White blood cell count may be increased or decreased. Other laboratory findings include hyponatremia, elevated AST and CK enzymes, prolonged PT and aPTT and decreased fibrinogen. Diagnosis is by serologic testing for both IgM and IgG RMSF antibodies. Antibody response may not be detected in the first 7 to10 days after illness onset. Treatment should not be delayed because of an initially negative result. PCR testing for RMSF is not reliable since the organism is predominantly found in endothelial cells and not circulating in peripheral blood.

Tularemia is a zoonotic infection caused by the gram-negative bacterium Francisella tularensis. Tularemia has variable symptoms but usually manifests with fever, flu-like illness, and lymphadenopathy. Route of infection is likewise variable and may include tick bites, as well as cat bites and other animal exposures. Diagnosis can be made by testing for Francisella tularensis antibody or by culture of blood or infected tissues, such as wounds or lymph nodes. Clinicians should notify the microbiology laboratory at the time of culture submission when tularemia is the suspected diagnosis, so that appropriate bacterial media can be utilized and precautions can be taken to avoid laboratory exposure to the organism.

Ehrlichiosis and anaplasmosis are closely related diseases caused by small, obligate intracellular bacteria, similar to rickettsia. Ehrlichia chaffeensis and Anaplasma phagocytophilum are the causative agents of human monocytic ehrlichiosis and human granulocytic anaplasmosis, respectively. Transmission is through tick vectors Amblyomma americanum (Lone Star tick) or Ixodes scapularis (deer tick or blacklegged tick), which is also associated with Lyme disease. Incubation period between tick bite and disease onset is generally 5 to 21 days.

Symptoms of ehrlichiosis and anaplasmosis are nonspecific including fever, malaise, and headache. Secondary symptoms of anorexia, nausea, vomiting, diarrhea, and abdominal pain are more frequent in ehrlichiosis. Serious complications include hypotension, respiratory failure, meningoencephalitis, acute renal failure and coagulopathy. Laboratory findings include leukopenia, thrombocytopenia, and elevated hepatic transaminases. CSF often shows elevated protein and lymphocytosis.

Recommended testing for ehrlichiosis and anaplasmosis includes serology and PCR. Serology includes IgG and IgM antibody for both organisms. Since both IgM and IgG antibodies may be negative during the first 7 to 14 days of infection, PCR is recommended for suspected acute disease. Examination of peripheral blood smears for morulae has a sensitivity of 20% and is not recommended as a diagnostic test.  Blood cultures do not detect these bacteria.

Lyme disease, due to Borrelia burgdorferi, is the most common tick-transmitted disease in the United States. A B. burgdorferi carrying tick has to be attached for at least 36 hours in order for the bacteria to be efficiently transmitted to an individual. Following transmission, the incubation period is typically 7 to 14 days, but can range from 3 to 32 days. The first phase of infection is the appearance of a erythema migrans rash, which occurs in approximately 80% of individuals. Some patients may also experience fatigue, malaise, myalgia, headache, and lymphadenopathy. During the next few weeks, untreated individuals may develop neurologic disease including meningitis, cranial neuropathy, and motor or sensory radiculoneuropathy. Patients may develop Bell’s Palsy and a oligoarticular arthritis involving the large joints.

Available testing for Lyme disease includes Lyme total antibody, which reflexes to Western blot confirmation when positive, as well as Lyme PCR for suspected acute infections. A negative result does not exclude Lyme disease, especially if the sample was collected within 2 weeks of symptom onset. If Lyme disease is strongly suspected, a second specimen should be tested 4 to 6 weeks after the first. Early administration of antibiotics may weaken or delay the antibody response.

Babesiosis is a malaria-like illness caused by the intraerythrocytic protozoan Babesia microti. Babesiosis is usually a tickborne illness but can also be transmitted by blood transfusion and transplacental spread. Ixodes scapularis tick is the vector for Babesia microti. Transmission requires 24 to 72 hours of attachment to a host. Babesia species cause illness by lysing erythrocytes, with resultant cytokine release. Symptoms usually appear 1 to 4 weeks after transmission and are nonspecific. Physical findings may include splenomegaly, hepatomegaly, jaundice, petechiae and ecchymosis. Laboratory findings include thrombocytopenia, hemolytic anemia, elevated liver enzymes and prolonged coagulation tests.

The diagnosis of babesiosis is most commonly made by finding the intraerythrocytic ring form of the organism (trophozoite) on Giemsa or Wright-stained blood smears. PCR can detect Babesia infection with negative blood smears.

Powassan virus is a flavivirus carried by Ixodes scapularis ticks. The most common presentation is viral encephalitis. Rash and GI symptoms may also occur. Testing for POWV infection is not usually included in arbovirus encephalitis panels and must be requested specifically. Serum and cerebrospinal fluid can be tested for anti-POWV IgM by immunoassay. Positive results are confirmed with a POWV neutralization test or detection of IgG antibody.

Two new viruses, Heartland and Bourbon, have been discovered in Missouri and Kansas patients. These viruses are believed to be transmitted by tick bites. Symptoms may be nonspecific including fever, anorexia and diarrhea. Laboratory findings include leukopenia, thrombocytopenia & elevated liver transaminases. Testing for Heartland and Bourbon viruses is available only through the CDC. The appropriate state health department must be contacted with case specifics to obtain testing.

Some ticks transmit more than one type of infection and, therefore, coinfection with multiple pathogens is possible. Coinfection may increase he severity of disease.  For example, Ixodes scapularis tick can transmit the organisms responsible for Lyme disease, anaplasmosis, babesiosis and Powassan infection.

Reference

Eickhoff C and Blaylock Jason, Tickborne diseases other than Lyme in the United States. Cleveland Clinic J Med. July 2017;84:555 – 567.

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fvplapp@icloud.com (Fred Plapp) Blog Sun, 13 Aug 2017 20:53:53 -0400
Four Ps of Thrombophilia Testing http://www.clinlabnavigator.com/four-ps-of-thrombophilia-testing.html http://www.clinlabnavigator.com/four-ps-of-thrombophilia-testing.html

Venous thromboembolism (VTE) is a major cause of morbidity and mortality. Approximately 900,000 cases of pulmonary embolism and deep vein thrombosis occur in the United States each year, causing 60,000 to 300,000 deaths.

Once a diagnosis of VTE has been established, physicians must decide if additional thrombophilia testing is warranted. One thoughtful approach to testing is the 4 Ps which include:

  • Patient selection
  • Pretest counseling
  • Proper laboratory interpretation
  • Provision of education and advice

The first step in patient selection is to determine if the VTE was provoked or unprovoked. Provoked VTE are due to known, temporary risk factors such as surgery, trauma, fracture, long distance travel, hormone therapy, malignancy, chemotherapy, rheumatologic disease, nephrotic syndrome, central venous catheter and inferior vena cava filter. Testing for thrombophilia should not be performed in these cases. Testing should also not be ordered if the patient is already receiving indefinite anticoagulation therapy and additional testing will not change the management plan. Thrombophilia testing may be considered in patients with unprovoked VTE, especially if VTE occurs in unusual sites or causes recurrent pregnancy loss.  Patients with unprovoked VTE have a twofold higher risk of recurrence than patients with provoked VTE.

Even in cases of unprovoked VTE, there is no clear consensus regarding which patients should be tested for thrombophilia. Experts recommend that patients who express a desire to be tested receive pretest counseling. The implications of finding a genetic diagnosis should be reviewed with the patient and family members. The American Board of Internal Medicine’s Choosing Wisely campaign strongly recommends consultation with an expert in thrombophilia prior to ordering testing. 

Proper test interpretation includes selection of the correct thrombophilia tests. Ordering large hypercoagulability panels is discouraged. Specimens for initial testing should be collected at the proper time. This means not testing during acute episodes of VTE or during anticoagulation therapy. Direct oral anticoagulants can cause false negative or false positive results with many thrombophilia tests. Testing should not be performed during pregnancy or treatment with oral contraceptives. Many hospitals forbid inpatient thrombophilia testing. If one of the initial tests is abnormal, guidance should be provided to insure that appropriate confirmatory tests are ordered.

Patients and family members should be provided with education at an appropriate health literacy level that explains the meaning of their test results and how it will affect their future care. While positive results may help to explain why a patient experienced an unprovoked VTE, they can also cause unnecessary worry about having a genetic disease and the risk of death.

More comprehensive information is available in an excellent review article that was recently published by physicians at the Cleveland Clinic.

Rendon P. et al. Optimizing diagnostic testing for venous thromboembolism. Cleveland Clinic Journal of Medicine, July 2017;84:545-554.

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fvplapp@icloud.com (Fred Plapp) Blog Sun, 23 Jul 2017 20:43:40 -0400
Eculizumab Associated Meningitis http://www.clinlabnavigator.com/eculizumab-associated-meningitis.html http://www.clinlabnavigator.com/eculizumab-associated-meningitis.html

Eculizumab (Soliris, Alexion Pharmaceuticals) is a recombinant humanized monoclonal antibody (IgG2/4 kappa) that was designed to block the activation of terminal complement components. It is licensed in the United States for treatment of paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome.

Eculizumab binds to the terminal complement protein C5, inhibiting its cleavage into C5a and C5b, thereby preventing the release of the inflammatory mediator C5a and the formation of the cytolytic pore C5b–C9. Blockade of the complement cascade at C5 preserves the early components of complement that are essential for the opsonization of microorganisms and clearance of immune complexes. In spite of this molecular design, recent evidence indicates that patients treated with eculizumab have a 1000 to 2000-fold increased incidence of meningococcal disease, even if they have received meningococcal vaccination. Food and Drug Administration (FDA)–approved prescribing information includes a boxed warning regarding increased risk for meningococcal disease in eculizumab recipients.

The majority of cases are caused by nongroupable Neisseria meningitidis and occur in patients who received at least 1 dose of meningococcal vaccine before disease onset. Nongroupable N. meningitidis is often carried asymptomatically in the nasopharynx, but it rarely causes disease in healthy persons.

The Advisory Committee on Immunization Practices recommends both MenACWY and MenB vaccination for patients taking eculizumab. MenACWY vaccines target the serogroup-specific polysaccharide capsule and provide no protection against nongroupable N. meningitidis. MenB vaccines are licensed specifically for protection against serogroup B meningococcal disease. Available evidence suggests that eculizumab interferes with the ability of anti-meningococcal antibodies to protect against invasive disease. Many clinicians and public health agencies recommend antimicrobial prophylaxis with penicillin for the duration of eculizumab treatment. Long-term penicillin prophylaxis is generally considered to be safe.

Neither vaccination nor antimicrobial prophylaxis can be expected to prevent all cases of meningococcal disease in eculizumab recipients.  Health care providers should have a high index of suspicion for meningococcal disease in patients taking eculizumab who develop any symptoms consistent with either meningitis or meningococcemia, even if the patient’s symptoms initially appear mild, and even if the patient has been fully vaccinated or is receiving antimicrobial prophylaxis.

Lucy A. McNamara, PhD; Nadav Topaz, MSc; Xin Wang, PhD; Susan Hariri, PhD; LeAnne Fox, MD; Jessica R. MacNeil, MPH. High Risk for Invasive Meningococcal Disease Among Patients Receiving Eculizumab (Soliris) Despite Receipt of Meningococcal Vaccine. MMWR Weekly / July 14, 2017 / 66(27);734-737.

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fvplapp@icloud.com (Fred Plapp) Blog Sun, 16 Jul 2017 19:26:36 -0400
Price Transparency for Laboratory Tests Does Not Change Physician Ordering Behavior http://www.clinlabnavigator.com/price-transparency-for-laboratory-tests-does-not-change-physician-ordering-behavior.html http://www.clinlabnavigator.com/price-transparency-for-laboratory-tests-does-not-change-physician-ordering-behavior.html

A recent randomized clinical trial studied the effect of providing physicians the Medicare allowable fees for inpatient laboratory tests on their ordering behavior. The Pragmatic Randomized Introduction of Cost data through the electronic health record (PRICE) included 98,529 patients comprising 142,921 admissions at 3 Philadelphia hospitals between April 2014 and April 2016. Inpatient laboratory test groups were randomly assigned to either display or not display Medicare allowable fees in the electronic health record. The primary outcome was the number of tests ordered per patient day. Results were compared during a 1-year intervention to a 1-year preintervention period and were adjusted for patient demographics, insurance, disposition and comorbidity severity.

Displaying Medicare allowable fees for inpatient laboratory tests in the electronic health record at the time of ordering did not lead to a significant change in physician ordering behavior. I wonder if a different outcome would have been achieved if the authors had displayed hospital charges for inpatient lab tests, which may be up to 40 times higher than Medicare allowable fees?

Sedrak MS et al. JAMA Intern Med. doi:10.1001/jamainternmed.2017.1144

Published online April 21, 2017.

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fvplapp@icloud.com (Fred Plapp) Blog Sun, 09 Jul 2017 21:26:20 -0400
Low Hemoglobin A1c Linked to Poor Prognosis http://www.clinlabnavigator.com/low-hemoglobin-a1c-linked-to-poor-prognosis.html http://www.clinlabnavigator.com/low-hemoglobin-a1c-linked-to-poor-prognosis.html

Hemoglobin A1c (HbA1c) is associated with poorer prognosis in patients with advanced liver disease. Approximately 40% of patients with cirrhosis and 20% of patients with hepatic fibrosis have HbA1c levels below 4.5%. Several studies have demonstrated that a HbA1c level below 5% is associated with increased risk of all-cause mortality. A J-shaped association exists between HbA1c and abnormal liver enzymes, hepatic steatosis, hospitalization due to liver disease and all-cause mortality, with the nadir of the curve at 4.7 to 5.5%. HbA1c levels above and below this range are both associated with increased health risks.

Low HbA1c levels in advanced liver disease may be caused by impaired glucose and insulin metabolism, depressed erythropoiesis, decreased protein synthesis, and/or shortened RBC survival. Extremely low HbA1c have clinical significance and should be investigated.

Ping Wang, Lab Med. 2017;48(1):89-92 

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fvplapp@icloud.com (Fred Plapp) Blog Tue, 04 Jul 2017 20:05:58 -0400
Hematology Hashtag Ontology for Pathologists http://www.clinlabnavigator.com/hematology-hashtag-ontology-for-pathologists.html http://www.clinlabnavigator.com/hematology-hashtag-ontology-for-pathologists.html

Twitter is becoming an increasingly valuable tool for discovery of fascinating case studies, communicating with colleagues and keeping abreast of the most recent advancements in all subspecialties of Pathology.  In March 2017, ClinLabNavigator published a list of Pathology Tag Ontology, which was developed by the USCAP Social Media Subcommittee. This list contained standardized hashtags for most subspecialties of pathology and laboratory medicine. On May 8, 2017, Hematology Tag Ontology was published on Symplur.com. This list contains many hashtags that will be of interest to pathologists and laboratory medicine professionals. They are separated by category and summarized below.

Bleeding

#BleedingDisorders bleeding disorders
#Hemophilia Hemophilia

Bone Marrow Failure

#BMFSM bone marrow failure

Coagulation / Clotting / Thrombosis

#VTE Venous Thromboembolism

Infections & immunodeficiencies

#Autoimmune autoimmune disease
#HIV HIV
#IDOnc Infectious Diseases Oncology
#ImmunoOnc Immuno-Oncology

Malignant Hematology

#Amyloidosis Amyloidosis
#BPDCN Blastic plasmacytoid dendritic cell neoplasm
#leusm Leukemia
#lymsm Lymphoma
#mdssm Myelodysplastic Syndromes
#MMSM Multiple Myeloma
#mpnsm Myeloproliferative Neoplasms
#wmsm Waldenström macroglobulinemia

Platelets

#PlateletRichPlasma Platelet Rich Plasma

Red Blood Cells (RBCs)

#anemia Anemia
#Thalassemia Thalassemia
#transfusion transfusion

Sickle Sell Disease (SCD)

#SickleCell Sickle Cell Disease

Transplantation & Cellular Therapy

#bmtsm blood and marrow transplantation
#GvHD Graft-versus host disease
#tcellrx T Cell Rx

Von Willebrand Disease (VWD)

#VWD von Willebrand disease

White Blood Cells (WBCs)

#Mastocytosis mastocytosis

 

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fvplapp@icloud.com (Fred Plapp) Blog Sun, 25 Jun 2017 20:29:02 -0400
Asymptomatic Microscopic Hematuria http://www.clinlabnavigator.com/asymptomatic-microscopic-hematuria.html http://www.clinlabnavigator.com/asymptomatic-microscopic-hematuria.html

Asymptomatic microscopic hematuria (AMH) is a common problem that can occasionally be a marker of severe disease such as urinary tract cancer. AMH is defined as 3 or more red blood cells per high-powered field on urine microscopy. In patients who have reasons for microscopic hematuria such as menstruation, urinary tract infection or recent instrumentation, testing should be repeated after these conditions have resolved. Most guidelines recommend that AMH should be based on 2 of 3 positive microscopic urinalyses to reduce the rate of false positive results. Diagnosis should not be based on urine dipstick analysis, which has a higher false positive rate.

In one large study of more than 20,000 asymptomatic adults with no history of urologic disease, AMH was found in 598 (3%) of cases using urine dipstick screening. Only 3 of these patients (0.5%) developed urologic cancer during the following 3 years. Two of cancers were prostate and one was bladder.

No professional medical organization recommends screening asymptomatic women or men with urine tests for detection of urinary tract cancer. The US Preventive Services Task Force (USPSTF) recommends against screening.

References

Subak LL & Grady D. Asymptomatic microscopic hematuria – rethinking the diagnostic algorithm. JAMA June 2017;177:808-09.

Halpern JA, Chughtai B, Ghomrawi H. Cost effectiveness of common diagnostic approaches for evaluation of asymptomatic microscopic hematuria. JAMA, published on line April 17, 2017.

Hiatt RA & Ordonez JD. Dipstick urinalysis screening, asymptomatic microhematuria and subsequent urological cancers in a population based sample. Cancer Epidemiol Biomarkers Prev 1994;3:439-443.

Moyer VA. US Preventive Services Task Force. Screening for bladder cancer. Ann Intern Med 2011;155:246-51.

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fvplapp@icloud.com (Fred Plapp) Blog Sun, 18 Jun 2017 20:18:04 -0400
Malaria in the United States http://www.clinlabnavigator.com/malaria-in-the-united-states.html http://www.clinlabnavigator.com/malaria-in-the-united-states.html

Malaria parasites of the Plasmodium genus are transmitted through the bite of infective female Anopheles mosquitoes. Four Plasmodium species commonly cause illness in humans: P. falciparum, P. vivax, P. ovale, and P. malariae. Mixed infections with multiple species might occur in areas where more than one species is in circulation. Rarely, humans can be infected with P. knowlesi, which is a simian malaria found in Southeast Asia. 

P. falciparum has the highest prevalence in sub-Saharan Africa. It is the most pathogenic malaria species and is most commonly associated with severe illness and death. P. vivax is less prevalent in sub-Saharan Africa because much of the population lacks the Duffy antigen required for P. vivax invasion of red blood cells. Because of its ability to survive at lower temperatures and higher elevations, P. vivax has a broader geographic range than P. falciparum. It accounts for 41% of malaria infections occurring outside the African continent.

Malaria relapses are common with P. vivax and P. ovale parasites, which have dormant liver stages (hypnozoites) that can reactivate months or years after the acute infection. P. malariae parasites mature slowly in human and mosquito hosts and, although they do not typically cause severe symptoms, they can result in persistent low-density infections that can last for years or even a lifetime 

Clinical illness results from the asexual intraerythrocytic stage of the parasite. Malaria symptoms vary, but the majority of patients have fever. Symptoms associated with uncomplicated malaria include chills, sweating, headache, fatigue, myalgia, cough, and nausea. If not treated promptly, malaria can affect multiple organ systems and result in altered consciousness, renal and liver failure, respiratory distress, coma, permanent disability, and death. 

In 2013, malaria was endemic in a total of 97 countries and territories in the tropics and subtropics. An estimated 198 to 214 million cases of malaria occurred worldwide, resulting in approximately 500,000 deaths. The majority of malaria infections in the United States occur among persons who have traveled to regions with ongoing malaria transmission. Occasionally, malaria is acquired by persons who have not traveled out of the country through transfusion with infected blood products, congenital transmission, laboratory exposure, or local mosquito-borne transmission.

In 2014, CDC received reports of 1,724 confirmed malaria cases, including one congenital case and two cryptic cases. Plasmodium falciparum, P. vivax, P. ovale, and P. malariae were identified in 66.1%, 13.3%, 5.2%, and 2.7% of cases, respectively. Less than 1.0% of patients were infected with two species. Among all reported cases, 17.0% were classified as severe illness, and five persons with malaria died.

CDC received 137 P. falciparum-positive samples for the detection of antimalarial resistance markers. Of the 137 samples tested, 131 (95.6%) had genetic polymorphisms associated with pyrimethamine drug resistance, 96 (70.0%) with sulfadoxine resistance, 77 (57.5%) with chloroquine resistance, three (2.3%) with mefloquine drug resistance, one (<1.0%) with atovaquone resistance, and two (1.4%) with artemisinin resistance.

The overall trend of malaria cases has been increasing since 1973; the number of cases reported in 2014 is the fourth highest annual total since then. Despite progress in reducing global prevalence of malaria, the disease remains endemic in many regions and use of appropriate prevention measures by travelers is still inadequate.

Malaria should be included in the differential diagnosis for every patient with fever who has traveled to an area where malaria is endemic. If malaria is suspected, both thick and thin Giemsa-stained blood smears should be examined by microscopy for parasites as soon as possible. Microscopy can quickly detect the presence of malaria parasites and determine the species and percentage of red blood cells that are infected. This information is essential to guiding treatment.

The BinaxNOW malaria rapid diagnostic test (RDT, Inverness Medical Professional Diagnostics, Scarborough, Maine, USA) detects circulating malaria-specific antigens and is approved for use by hospital and commercial laboratories. RDTs can decrease the amount of time required to determine whether a patient is infected with malaria but does not eliminate the need for standard blood smear examination. RDTs are not able to fully speciate or quantify malaria parasites. Positive and negative RDT results must be confirmed by microscopy. If microscopy is not performed, PCR can be performed to confirm an RDT result and determine the species.

PCR cannot be performed quickly enough to be of use in the initial diagnosis and treatment of acute malaria, but is useful to confirm the species and to guide treatment. PCR is available in reference and health department laboratories. CDC recommends that PCR be performed for all cases of malaria to confirm the infecting species.

Reference

CDC. Malaria Surveillance-United States, 2014. MMWR Surveillance Summaries, May 26, 2017;66(12)1-24.

 

 

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fvplapp@icloud.com (Fred Plapp) Blog Sun, 11 Jun 2017 18:18:31 -0400