Blog Mon, 26 Jun 2017 12:45:32 -0400 Joomla! - Open Source Content Management en-gb Hematology Hashtag Ontology for Pathologists

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 This list contains many hashtags that will be of interest to pathologists and laboratory medicine professionals. They are separated by category and summarized below.


#BleedingDisorders bleeding disorders
#Hemophilia Hemophilia

Bone Marrow Failure

#BMFSM bone marrow failure

Coagulation / Clotting / Thrombosis

#VTE Venous Thromboembolism

Infections & immunodeficiencies

#Autoimmune autoimmune disease
#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


#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


]]> (Fred Plapp) Blog Sun, 25 Jun 2017 20:29:02 -0400
Asymptomatic Microscopic Hematuria

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.


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.

]]> (Fred Plapp) Blog Sun, 18 Jun 2017 20:18:04 -0400
Malaria in the United States

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.


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



]]> (Fred Plapp) Blog Sun, 11 Jun 2017 18:18:31 -0400
Amanita Phalloides Mushroom Poisoning

Amanita phalloides, colloquially known as the “death cap,” belongs to the Phalloideae section of the Amanita family of mushrooms and is responsible for most deaths following ingestion of foraged mushrooms worldwide.

A. phalloides contains the alpha variety of amanitin, a cyclic octapeptide thought to be the primary agent of toxicity in humans. The amanitins are heat stable and are not inactivated by cooking. A lethal dose can be as low as 0.1 mg/kg, and a single mushroom can contain up to 15 mg. Once ingested, amatoxin is readily absorbed from the gastrointestinal tract into the portal circulation where it is taken up by hepatocytes. Amatoxin binds to DNA-dependent RNA polymerase (II) and inhibits protein synthesis, ultimately resulting in cell death.

The clinical course of amatoxin poisoning is described in three phases:

  • Delayed gastroenteritis with significant body fluid volume loss within 6 to 24 hours after ingestion
  • Symptomatic recovery within 24 to 36 hours after ingestion
  • Fulminant hepatic and multiorgan failure 3 to 5 days after ingestion.

Patients who are evaluated early in the course of their illness might be discharged home only to return later with indications of liver failure, contributing to the relatively high case fatality rate of 10% to 20%.

Liver enzymes begin to rise 24 to 36 hours after ingestion. Progressive liver disease results in elevated bilirubin, prothrombin time, and ammonia. Development of hepatorenal syndrome is accompanied by acidosis, hypoglycemia and renal failure. Vomiting and diarrhea cause electrolyte abnormalities. Analysis of specific mycotoxins is not usually available quickly enough to be clinically valuable.

Initial treatment includes early supportive care including aggressive fluid and electrolyte replacement. In the event of irreversible fulminant liver failure, liver transplant might be required. A variety of therapies including multidose activated charcoal, high-dose penicillin, N-acetylcysteine, cimetidine, biliary drainage, and octreotide have been attempted with no definitive evidence of efficacy.


  1. Wieland T, Wieland O. Chemistry and toxicology of the toxins of Amanita phalloides Pharmacol Rev 1959;11:87–107. PubMed
  2. Wieland T. The toxic peptides from Amanita mushrooms. Int J Pept Protein Res 1983;22:257–76.  CrossRef PubMed
  3. Olson KR, Pond SM, Seward J, Healey K, Woo OF, Becker CE. Amanita phalloides-type mushroom poisoning. West J Med 1982;137:282–9. PubMed
  4. Vo KT et al. Amanita phalloides Mushroom Poisonings – Northern California, December 2016, MMWR June 2, 2017;66:549-53
]]> (Fred Plapp) Blog Sun, 04 Jun 2017 20:27:03 -0400
Hepatitis C Virus Testing Guidelines

Many people with Hepatitis C virus (HCV) do not know they are infected. Since many people can live with HCV for decades without developing symptoms, testing is critical. HCV infection can progress to cirrhosis and hepatocellular carcinoma. Highly effective medications are now available that can cur HCV infection.

The Center for Disease Control and Prevention (CDC) recommends testing the following individuals for HCV infection:

  • Adults born from 1945 through 1965 should be tested at least once in their lifetime and more frequently if they are at ongoing risk
  • Persons who currently or previously inject drugs
  • Patients who have HIV infection
  • Patients with persistently abnormal alanine aminotransferase (ALT) levels
  • Patients treated with clotting factor concentrates produced before 1987
  • Patients who have ever received long-term hemodialysis
  • Patients who were recipients of either blood transfusions or organ transplants before July 1992, or who were notified their donor later tested positive for HCV
  • Children born to HCV-positive women
  • Healthcare, emergency medical, and public safety workers with exposure to HCV-positive blood through needle sticks, sharps, or mucosal exposures

CDC also suggests that HCV testing may benefit:

  • Recipients of transplanted tissues
  • Persons who inject drugs
  • Intranasal cocaine and other non-injecting illegal drug users
  • Persons with a history of tattooing or body piercing
  • Persons with a history of multiple sex partners or sexually transmitted infections
  • Long-term steady sex partners of HCV-positive persons
  • Persons who engage in high-risk sexual activity and with history of sexually transmitted infections

The initial test should be an immunoassay for HCV antibody. Individuals with reactive test results should be confirmed with quantitative real-time PCR for HCV RNA. Patients, who have confirmed positive results for HCV infection, should then have their HCV genotype determined. If an individual has HCV genotype 1a, they should be further tested for NS5a drug resistance.

All patients with chronic HCV infection should be tested for evidence of current or previous Hepatitis B (HBV) infection by measuring Hepatitis B surface antigen (HBsAg) and Hepatitis B core antibody (anti-HBc). This testing should be completed before initiating HCV treatment because HBV may be reactivated.


CDC Testing Recommendations for Hepatitis C Virus Infection:

]]> (Fred Plapp) Blog Sun, 21 May 2017 21:32:43 -0400
IgA Vasculitis

IgA vasculitis affects small blood vessels and typically causes petechiae and purpura that is not accompanied by thrombocytopenia or coagulopathy. It was previously called Henoch Schonlein purpura. IgA vasculitis occurs most commonly in children between the ages of 3 and 15 years of age and is often preceded by upper respiratory tract infections. The majority of cases are self limited and require no specific therapy.

The classical triad in children includes:

  • Palpable purpura without thrombocytopenia or coagulopathy
  • Abdominal pain
  • Arthritis or arthralgia
  • Renal disease causing proteinuria and hematuria

In contrast to other vasculitides, most cases of IgA vasculitis begin with the onset of cutaneous lesions prior to other manifestations. Approximately two thirds of children develop gastrointestinal and renal involvement. Gastrointestinal involvement is usually characterized by colicky abdominal pain that often resembles an acute abdomen. IgA vasculitis most often involves the large joints of the legs, but any joint can be involved.

The diagnosis of IgA vasculitis is usually based on clinical manifestations. Serum IgA levels are elevated in 50 to 75% of cases, especially those with renal involvement. Onset of IgA vasculitis after a respiratory tract infection is often associated with decreased levels of complement C3 and C4. Platelet count and coagulation tests are normal. Tests for autoantibodies such as ANA and ANCA are negative. Skin biopsy reveals leukocytoclastic vasculitis involving postcapillary venules within the papillary dermis with predominant IgA deposition. It is important to note that IgA deposition may also be seen in leukocytoclastic vasculitis that is due to cryoglobulinemia or the use of certain medications, including tumor necrosis factor (TNF) alpha inhibitors.

Jennette JC et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 2013:65:1.

Piram M, Marh A. Epidemiology of immunoglobulin A vasculitis (Henoch-Schonlein): current state of knowledge. Curr Opin Rheumatol 2013;25:171. 

]]> (Fred Plapp) Blog Sun, 14 May 2017 20:48:32 -0400
Preeclampsia Screening Should Not Include Proteinuria

Preeclampsia affects approximately 4% of pregnancies in the United States. Preeclampsia is defined as the onset of hypertension occurring after 20 weeks of gestation, combined with either proteinuria or other signs or symptoms involving multiple organ systems. Preeclampsia causes adverse health effects in both mothers and infants. Serious maternal complications include stroke, retinal detachment, HELLP syndrome and eclampsia. The latter can cause maternal brain damage, aspiration pneumonia, pulmonary edema, placental abruption, disseminated coagulopathy, acute renal failure, cardiopulmonary arrest, and coma. Adverse perinatal outcomes for the fetus and newborn include intrauterine growth restriction, oligohydramnios, low birth weight, and stillbirth. Preeclampsia leads to early induction of labor or cesarean delivery and subsequent preterm birth.

The United States Preventive Services Task Force (USPSTF) recently updated their recommendation on screening for preeclampsia during pregnancy. USPSTF found that screening and early treatment reduce maternal and perinatal morbidity and mortality. USPSTF recommends screening for preeclampsia with blood pressure measurements throughout pregnancy. The agency did not find sufficient evidence to support point of care urine testing for proteinuria. Urine dipstick tests for proteinuria had sensitivity ranging from 0.22 to 1.00 and specificity ranging from 0.36 to 1.00. Sensitivity of the protein to creatinine ratio ranged from 0.65 to 0.96 and specificity ranged from 0.49 to 1.00. These performance statistics were obtained by screening women with preeclampsia and not all pregnant women. 

According to USPSTF, proteinuria measurement should be reserved for diagnosis of preeclampsia. Recently revised criteria for the diagnosis of preeclampsia include; elevated blood pressure (140/90 mm Hg or greater on 2 occasions after 20 weeks of gestation) and proteinuria, which is defined as 300 mg/dL of protein or greater in a 24 hour urine collection or a protein to creatinine ratio of 3 mg/g or greater. If quantitative analysis is not available, a urine protein dipstick reading of >1 can be substituted. If proteinuria is not present, then the presence of thrombocytopenia, renal insufficiency, abnormal liver function, pulmonary edema, and cerebral or visual symptoms can be used to make the diagnosis.

USPSTF’s revised recommendation is similar to the recommendation of the American College of Obstetricians and Gynecologists. ACOG recommends obtaining blood pressure measurements at every prenatal visit and using a detailed medical history to evaluate for risk factors for preeclampsia.

US Preventive Services Task Force, Screening for Preeclampsia. JAMA 2017;317:1661-67.

American College of Obstetricians and Gynecologists. Hypertension in Pregnancy. Washington, DC: American College of Obstetricians and Gynecologists; 2013. 

]]> (Fred Plapp) Blog Sun, 07 May 2017 21:05:41 -0400
Undetectable HDL Cholesterol

Very low or undetectable HDL cholesterol can be caused by paraprotein interference with the direct homogeneous assay or the development of autoantibodies to apoA1, which is the primary protein in HDL particles. Drug therapy with fibrates, anabolic steroids and thiazolidinediones can also drastically reduce HDL cholesterol. Genetic diseases such as Tangier disease, apoA-1 deficiency and LCAT deficiency are associated with very low HDL cholesterol levels.

More recently, a case study published in the February issue of Clinical Chemistry described a patient with undetectable HDL cholesterol that was associated with Babesiosis microti infection. HDL cholesterol returned to normal following antibiotic therapy and resolution of the infection. The authors suggest that the production of interleukin 10 disturbs lipoprotein metabolism and produces acquired HDL deficiency. However, they acknowledge that undetectable HDL is an unusual finding relative to the numbers of severe sepsis cases. Alternatively, Babesia may directly interfere with HDL cholesterol synthesis.

Bock JL, Senzel L, Spitzer ED and Bifulco W. Undetectable HDL Cholesterol in a Patient with Flu-Like Illness. DOI: 10.1373/clinchem.2016.258616 Published February 2017.

]]> (Fred Plapp) Blog Sun, 30 Apr 2017 20:14:33 -0400
Foodborne Illnesses in 2016

Foodborne illness remains a substantial public health concern in the United States. FoodNet is a collaboration among CDC, 10 state health departments, the U.S. Department of Agriculture’s Food Safety and Inspection Service, and the Food and Drug Administration. FoodNet conducts active, population-based surveillance for laboratory-diagnosed infections caused by nine enteric pathogens including; Campylobacter, Cryptosporidium, Cyclospora, Listeria, Salmonella, Shiga toxin-producing Escherichia coli (STEC), Shigella, Vibrio, and Yersinia. Surveillance covers 10 sites representing approximately 15% of the U.S. population.

During 2016, FoodNet identified 24,029 cases, 5,512 hospitalizations, and 98 deaths attributed to foodborne illness. Infections were detected by culture or culture-independent diagnostic tests (CIDT). Parasitic infections were detected in clinical specimens by direct fluorescent antibody test, polymerase chain reaction, enzyme immunoassay, or light microscopy. CIDTs included tests for bacterial antigens, nucleic acid sequences, or Shiga toxin in a stool specimen or enrichment broth. The largest number of culture confirmed or CIDT positive–only infections in 2016 was reported for Campylobacter (8,547), followed by Salmonella (8,172), Shigella (2,913), STEC (1,845), Cryptosporidium (1,816), Yersinia (302), Vibrio (252), Listeria (127), and Cyclospora (55).

The number of infections detected by CIDT has been steadily increasing compared to culture. Increased use of CIDT may account for the increased incidence of Cryptosporidium, STEC, and Yersinia, and slight but not significant increases in incidence of Campylobacter, Salmonella, Shigella, and Vibrio. More widespread adoption of CIDT is likely to improve detection of foodborne illness.


Marder EP, Cieslak PR, Cronquist AB, et al. Incidence and Trends of Infections with Pathogens Transmitted Commonly Through Food and the Effect of Increasing Use of Culture-Independent Diagnostic Tests on Surveillance — Foodborne Diseases Active Surveillance Network, 10 U.S. Sites, 2013–2016. MMWR Morb Mortal Wkly Rep 2017;66:397–403. DOI:

]]> (Fred Plapp) Blog Sun, 23 Apr 2017 20:21:08 -0400