Here we will discuss:
- von Willebrand’s disease
- Bernard-Soulier syndrome
- Glanzmann’s Thrombasthenia
- May–Hegglin anomaly (MHA)
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%)
* 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
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
DDAVP (desmopressin) if mild, and with vWF concentrate
- 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.
- 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
- 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%)
platelet glycoprotein IIb/IIIa complex is either deficient or present but dysfunctional leading to defective platelet aggregation and subsequent bleeding
- 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
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:
- May-Hegglin is Dominant because of Dohle and Giant platelets; remember also Alport is (x-lined) dominant
- Bernard-Soulier has 2 names ADHERED (adhesion problem); so it becomes Giant and do not listen to Ristocetin
- Glanzmann has “G” for AGGreGation and aGree to ristocetin while response to others are decreased
Btw, I want this [eafl id=”594″ name=”Amazon stetho” text=”stethoscope”] as my next gadget and daily driver.