Bernard-Soulier, Glanzmann, Uremia

Summary

Three classic platelet function disorders share a common picture: mucocutaneous bleeding (epistaxis, gum bleeding, easy bruising, menorrhagia) with a normal platelet count and a prolonged bleeding time / abnormal PFA-100.

• Bernard-Soulier syndrome (BSS): inherited deficiency of GPIb → platelets cannot bind vWF → defective adhesion.
• Glanzmann thrombasthenia: inherited deficiency of GPIIb/IIIa → platelets cannot bind fibrinogen → defective aggregation.
• Uremia: acquired platelet dysfunction in chronic kidney disease due to uremic toxins coating platelets and impairing function.

PT and aPTT are normal in all three (the coagulation cascade is intact).

Quick review of normal platelet function

Primary hemostasis happens in 3 steps. Each disorder breaks one specific step:

1. Adhesion — platelet GPIb binds vWF on exposed subendothelial collagen. Defective in Bernard-Soulier.
2. Activation — platelets release ADP, TXA2, and change shape. Defective in uremia (toxins block activation/release).
3. Aggregation — GPIIb/IIIa binds fibrinogen, linking platelets together. Defective in Glanzmann.

Bernard-Soulier syndrome (BSS)

Definition: Rare autosomal recessive deficiency or dysfunction of the GPIb-IX-V complex → platelets cannot bind vWF → cannot adhere to injured vessel wall.

Clinical features:

• Mucocutaneous bleeding from early childhood: epistaxis, gingival bleeding, easy bruising, menorrhagia.
• Severity is variable; can be life-threatening.

Labs (the classic triad):

• Mild thrombocytopenia (low count) — unusual feature for a "function" disorder.
• Giant platelets on peripheral smear (large MPV).
• Prolonged bleeding time / abnormal PFA-100; normal PT/aPTT.

Platelet aggregation studies:

• Absent response to ristocetin (mimics vWF binding to GPIb).
• Normal response to ADP, collagen, epinephrine, and arachidonic acid.
• Ristocetin response is not corrected by adding normal plasma (differentiates from vWD, where it is corrected).

Glanzmann thrombasthenia

Definition: Rare autosomal recessive deficiency or dysfunction of GPIIb/IIIa (integrin αIIbβ3) → platelets cannot bind fibrinogen → cannot aggregate.

Clinical features:

• Mucocutaneous bleeding from infancy: epistaxis (most common), gingival bleeding, GI bleeding, menorrhagia, post-circumcision bleeding.

Labs:

• Normal platelet count and normal size (different from BSS).
• Prolonged bleeding time; normal PT/aPTT.

Platelet aggregation studies:

• Absent aggregation with ADP, collagen, epinephrine, and thrombin.
• Normal ristocetin response (adhesion is intact — opposite of BSS).

Uremic platelet dysfunction

Definition: Acquired qualitative platelet defect in patients with chronic kidney disease (CKD), especially when BUN is markedly elevated.

Pathophysiology:

• Accumulated uremic toxins (urea, guanidinosuccinic acid) impair platelet activation and aggregation.
• Decreased vWF-platelet interaction and abnormal release of platelet granules.
• Anemia of CKD also contributes (platelets are pushed away from the vessel wall).

Clinical features:

• Mucocutaneous bleeding in a known CKD patient: ecchymoses, epistaxis, GI bleeding, prolonged bleeding after procedures (e.g., AV fistula creation).

Labs:

• Normal platelet count and normal PT/aPTT.
• Prolonged bleeding time.
• Elevated BUN/creatinine.

Side-by-side comparison

Management

Bernard-Soulier & Glanzmann (inherited):

• Local measures: compression, antifibrinolytics (tranexamic acid, aminocaproic acid) for mucosal bleeding.
• Platelet transfusion for severe bleeding or before surgery — main definitive therapy.
  • Risk: alloantibody formation against the missing glycoprotein → refractoriness to future transfusions.
• Recombinant factor VIIa if platelets are ineffective due to alloantibodies (especially Glanzmann).
• Avoid antiplatelet drugs (aspirin, NSAIDs).

Uremic platelet dysfunction (acquired):

• Dialysis — removes uremic toxins; first-line for chronic bleeding.
• Desmopressin (DDAVP) — releases vWF/factor VIII from endothelium; rapid onset (1–2 h), useful for acute bleeding or before procedures.
• Cryoprecipitate — supplies vWF/fibrinogen if DDAVP fails.
• Correct anemia with erythropoietin (target Hb ~10 g/dL) — improves platelet–vessel wall interaction.
• Conjugated estrogens for longer-lasting effect.

Mnemonics

Key Points for Exams – نقاط مهمة للامتحانات

• All three present with mucocutaneous bleeding + normal PT/aPTT + prolonged bleeding time / PFA-100.
• BSS: low platelets, giant platelets, absent ristocetin (not corrected by plasma).
• vWD vs. BSS: both fail ristocetin, but vWD is corrected by normal plasma; BSS is not.
• Glanzmann: normal count & size, normal ristocetin, absent ADP/collagen/epi aggregation.
• Uremia: the most common acquired platelet dysfunction; treat with dialysis + DDAVP, correct anemia.
• DDAVP works in: uremia, vWD (type 1), hemophilia A (mild). It does NOT work in BSS or Glanzmann.
• Avoid aspirin/NSAIDs in all platelet function disorders.
• Definitive treatment for severe inherited bleeding = platelet transfusion; beware alloimmunization.