Platelet Disorders

Platelet Disorders

von Willebrand’s disease

* the most common inherited coagulopathy caused by a defect in von Willebrand factor, which aids the binding of platelets to collagen
* chromosome 12, autosomal dominant
* Bleeding related to platelets (epistaxis, gingival, gums) with a normal platelet count;
* exacerbated by the use of aspirin
* it is a protective carrier for factor VIII; hence factor VIII may be low and hence aPTT may be elevated (50%)

Dx –

* low vWF (antigen) level;
* Ristocetin cofactor assay (or vWF activity) – detects vWF dysfunction; deficient ristocetin-induced platelet aggregation
* it means there is no response to ristocetin but this is corrected with the addition of normal plasma

* low factor VIIIc;
* prolonged BT

Scenario:
The combination of a petechial skin rash combined with a slightly elevated APTT and reduced factor VIII activity make Von Willebrand’s disease the most likely diagnosis, though hemophilia will be given in the answer choices

Tx –
DDAVP (desmopressin) if mild, and with vWF concentrate


Bernard-Soulier syndrome

  • autosomal recessive
  • disease of platelet adhesion which causes prolonged bleeding times in the presence of normal platelet counts.
  • These defective platelets cannot bind to subendothelial collagen properly because of a deficiency or dysfunction of the glycoprotein Ib-IX complex.
  • Dx
    • Clinically the patients have impaired hemeostasis and recurrent severe mucosal hemorrhage.
    • bleeding out of proportion to the degree of thrombocytopenia
    • mild thrombocytopenia, circulating “giant” platelets, severe platelet dysfunction; Hb may be low because of blood loss
    • platelets do not aggregate in response to ristocetin, but have a nornal aggregation in response to adenosine diphosphate (ADP), epinephrine and collagen
  • Tx
    • The only treatment for an acute episode is a transfusion of normal platelets.
    • Cryoprecipitate or vWF concentrate do not help

May–Hegglin anomaly (MHA)

  • May–Hegglin anomaly (MHA), also known as Dohle leukocyte inclusions with giant platelets and macrothrombocytopenia with leukocyte inclusions
  • autosomal dominant, MYH9 gene defect (22q12-13)
  • may found in association with Alport Syndrome
  • So, look for high frequency hearing loss (82%), proteinuria (40%), cataracts (25%), Hematuria (25%)

Glanzmann’s Thrombasthenia

autosomal recessive

platelet glycoprotein IIb/IIIa complex is either deficient or present but dysfunctional leading to defective platelet aggregation and subsequent bleeding

Dx

  • Platelet counts and other coagulation tests (PT, PTT) are normal
  • Prolonged BT
  • Primary platelet aggregation response to platelet agonists such as adenosine diphosphate, epinephrine, and collagen is decreased, while the response to ristocetin is normal

Tx

  • platelet transfusion in case of active bleeding

 

May-Hegglin anomaly is rare and not really tested in questions. Also, it is in fact primarily a morphology and quantitative platelet disorder but I put it as a side note to compare.

My way to remember:

  1. May-Hegglin is Dominant because of Dohle and Giant platelets; remember also Alport is (x-lined) dominant
  2. Bernard-Soulier has 2 names ADHERED (adhesion problem); so it becomes Giant and do not listen to Ristocetin
  3. Glanzmann has “G” for AGGreGation and aGree to ristocetin while response to others are decreased

 

 

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Diarrhea and Gastroenteritis

Diarrhea and Gastroenteritis

Definition:

Consistency is much more important than frequency to define diarrhea…

Types

Watery, osmotic (e.g, Laxative-induced diarrhea),

secretory (eg, microscopic colitis)

Functional – mucus (typically from irritable bowel syndrome)

Inflammatory – blood +/- pus (eg, IBD as in Chron’s and UC, some invasive bacteria)

Fat (steatorrhea)

Case Approach:

Two main questions to answer are:
  1. Acute or Chronic
  2. Watery (non-bloody) or Bloody

Blood and WBCs in stool

Salmonella: contaminated poultry and eggs; more common in patients with SCD and achlorhydria
 
Campylobacter jejuni: most common cause, rarely associated with GBS
 
E. coli  O157:H7 — undercooked hamburger meat; hemolytic uremic syndrome (HUS)
 
Shigella: 2nd most common association with HUS
 
Vibrio parahaemolyticus: shellfish and cruise ships
Vibrio vulnificus: raw shellfish, h/o liver disease, iron overload and bullous skin lesions
                          * may cause invasive, life-theratening disease in immunocompromised patients or those with liver disease
 
Yersinia enterocolitica: high affinity for iron, hemochromatosis, blood transfusions; can mimic appendicitis or Chron’s disease
               tends to infect the cecum rather than distal colon
 
Clostridium difficile:  previous antibiotic use;  white and red cells in stool
Clostridium botulinum :   infected canned foods
Clostridium perfringens:  meats taht have been contaminated with spores by being unrefrigerated
 The major protozoan associated with blood in the stool is Entamoeba histolytica.

No Blood and WBCs in stool

  • Viral
  • Giardia lamblia
  • Cryptosporidiosis/ isospora: AIDS with CD4 <50-100; detected by modified acid fast stain (treat underlying AIDS, nitazoxanide which is superior to paromomycin)
  • Bacillus cereus: vomiting –  warmed or slowly re-heated fried rice
  • Staphylococcus: vomiting
Dx
  • The best initial test is for  blood and/or fecal leukocytes with methylene blue testing
  • Stool lactoferrin has greater sensitivity and specificity compared with stool leukocytes
  • The most accurate test = stool culture to determine the specific type
  • Modified acid-fast test for cryptosporidiosis because routine fecal O/P does not reliably pick up
  • ELISA stool antigen test for Giardiasis (90% sensitivity); 3 fecal O/P for Giadria has lesser sensitivity (80%) than single stool antigen test
Tx
  • supportive
  • consider antibiotics only when abdominal pain, blood in the stool, and fever
  • best initial empirical = ciprofloxacin or other fluoroquinolones +/- metronidazole
  • TMP/SMX for Isopora
  • Doxycycline for Vibrio vulnificus
  • Rifaximin for traveler’s diarrhea

Giardia lamblia

  • flagellated protozoan, often acquired during hiking/ camping activities, by drinking unpurified water from streams
  • affects small bowel (duodenum and proximal jejunum) producing upper GI symptoms such as frequent burping, bloating, distention, flatus, and loose, nonbloody, foul-smelling and fatty diarrhea (steathorrhea).
Dx:
  • duodenal aspirate/ biopsy/ immunoassay
  • stool for parasites/ eggs
  • stool ELISA
Tx-
  •   metronidazole/ Tinidazole
**Giardiasis is the only common primary infection causing chronic malabsorption.

Pseudomembranous colitis

caused by C. difficile; Gram +ve superbug whose spores are contagious (fecal-oral or from the environment)
Girotra’s triad
  1. Increasing abdominal pain/distention and diarrhea
  2. Leukocytosis > 18,000
  3. Hemodynamic instability
Tx
  • Stop the causative antibiotic (if possible)
  • No treatment if asymptomatic
  • Metronidazole for symptomatic cases
  • Vancomycin may be better in severe disease
  • Consider surgery (urgent colectomy) if complications such as toxic megacolon developed; raised LDH and in deteriorating patient

Initial evaluation of Chronic diarrhea

Fat:
  • most useful screening test is stool for fat (Sudan red stain)
  • confirm with 72-hour stool for fecal fat (gold standard for steatorrhea)
  • Steatorrhea is most prominent with pancreatic insufficiency; all require a sweat chloride (to rule out CF and Schwachman-Diamond $)
  • Serum trypsinogen may also be used
  • Screen for carbohydrate malabsorption — measure reducing substances in stool (Clinitest)
  • Breath hydrogen test
  • Protein loss — difficult to evaluate directly
  • Screen with spot stool alpha-1 anti-trypsin level

Differential Diagnoses of Chronic Diarrhea

  1. most common infectious cause = Giadiasis
  2. most common congenital cause with malabsorption = cystic fibrosis
  3. most common anomaly cause with incomplete bowel obstruction + malabsorption= malrotation