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

 

 

Polycythemia

Polycythemia

Primary polycythemia/ Polycythemia vera

  • a.k.a polycythemia rubra vera; erythremia
  • common in age 60 – 75
  • overproduction of all three hematopoietic cell lines with predominant elevation in red cell counts
  • mutation in the JAK2 protein which regulates marrow production
  • red cells grow wildly despite a Low erythropoietin level
  • high serum leukocyte alkaline phosphate
features:
  • Headache, blurred vision, and tinnitus
  • pruritus, especially after hot bath (due to histamine release from increased numbers of basophils)
  • HTN, facial plethora, fatigue, Splenomegaly
  • Bleeding from engorged blood vessels
  • Thrombosis from hyperviscosity
Investigation,
  • elevated Hct >60%*
  • low MCV and Low iron (because of excessive usage and production)
  • however, Vit. B12 levels are elevated for unclear reason
  • exclude hypoxia first; normal Oxygen level and *low erythropoietin level in PV
* RCC also has elevated Hct, but the erythropoietin is elevated.
* A small number of patients can convert to AML.
Tx
  • initial 1st line – Phlebotomy and aspirin prevent thrombosis – target Hct 45%
  • Hydroxyurea helps lower the cell count
    • indicated in old age >70 years; has thrombosis; has a platelet count >1500; and has cardiovascular risk factors
  • Allopurinol or rasburicase protects against uric acid rise
  • Antihistamines
  • Interferon alpha may be used in refractory cases
Platelet counts elevate temporarily after spleen removal

Secondary polycythemia
Increased erythropoietin level
2° to chronic tissue hypoxia
 

Kidney cancer is an important differential diagnosis of secondary polycythemia.

Renal Cell Carcinoma is a neoplastic condition that can initially appear with many different paraneoplastic manifestations.

The initial presentation may include hypertension, flank mass, gross or microscopic hematuria, hypercalcemia, fever, weight loss, and/or polycythemia.

Polycythemia may be the presenting sign in 3% of cases of kidney cancer.

Careful evaluation is important in patients presenting with polycythemia and hematuria.

Polycythemia is secondary to a hypersecretion of tumor cytokines, including renin.

The patient’s erythropoietin level is usually high.

Surgical removal of the cancer resolves the polycythemia.