Functional Platelet Disorders

Bleeding with a normal platelet count. Suspect it when bleeding is out of proportion to the count and thrombocytopenia and coagulation factor deficiency have been excluded.

Bleeding risk depends on both count and function: when platelet function is reduced — by uraemia, aspirin, an NSAID, another drug, or an inherited condition — the risk of bleeding rises at any given count.

Bleeding pattern

Platelet problems are disorders of primary haemostasis, so the bleeding is mucocutaneous:

• Easy bruising.
• Epistaxis.
• Heavy menstrual bleeding.
• Gum bleeding, prolonged bleeding after dental work or minor surgery.

Contrast with secondary haemostasis (factor) disorders, which cause deep tissue haematomas and intracranial haemorrhage.

Causes

Inherited (rare, but probably underdiagnosed)

• Glanzmann thrombasthenia — GPIIb/IIIa defect, so platelets cannot aggregate.
• Bernard-Soulier syndrome — GPIb defect, so platelets cannot adhere to von Willebrand factor.
• Storage pool deficiency — δ-granule deficiency, grey platelet syndrome.
• Von Willebrand disease is the commonest inherited bleeding disorder overall (up to 1% of the population) and should be excluded first — it presents identically.

Drugs

• Aspirin irreversibly inhibits COX-1, blocking thromboxane A2 synthesis, so platelets cannot recruit and aggregate normally. The effect lasts the platelet’s 7–10 day lifespan.
• NSAIDs inhibit COX reversibly.
• P2Y12 inhibitors (clopidogrel, ticagrelor) block ADP-driven activation.
• GPIIb/IIIa inhibitors (abciximab, tirofiban) block aggregation directly.
• Also implicated: anticoagulants, tricyclic antidepressants, some antibiotics, herbal supplements.

Aspirin at therapeutic doses causes only a modest increase in bleeding in healthy people, but a markedly larger increase in older patients.

Systemic disease

• Uraemia / kidney failure — platelet count is normal but function is impaired.
• Myeloproliferative neoplasms and myelodysplastic syndrome.
• Dysproteinaemias — multiple myeloma, Waldenström macroglobulinaemia.
• Liver failure, cirrhosis.
• SLE.

Investigations

• FBC and film first — confirm the count is genuinely normal and exclude pseudothrombocytopenia (platelet clumping; repeat in a citrate tube).
• Coagulation screen and von Willebrand panel (factor VIII, vWF antigen, vWF activity) to exclude the commoner mimics.
• A structured bleeding-history tool such as the ISTH-BAT is more useful than any single test.
• PFA-100/200 — good screening test. Prolonged EPI/collagen closure time with a normal ADP/collagen time suggests aspirin, NSAIDs or other drugs; both prolonged suggests von Willebrand disease, Bernard-Soulier syndrome or Glanzmann thrombasthenia.
• Light transmission aggregometry — the gold standard, but slow, operator-dependent and only available in specialist centres.
• Flow cytometry for platelet membrane glycoproteins — diagnostic for Bernard-Soulier and Glanzmann.
• Electron microscopy for δ-storage pool deficiency and grey platelet syndrome.
• Bleeding time is obsolete — poorly standardised and reproducible, with low sensitivity, specificity and positive predictive value. It has been replaced by automated platelet function analysers.

Stop drugs, foods and supplements that affect platelet function for several days before platelet function testing, or results are uninterpretable.

Management

• Remove the cause where possible — stop the offending drug, dialyse the uraemic patient.
• Uraemic bleeding responds to dialysis, cryoprecipitate or desmopressin.
• Desmopressin also works in type 1 von Willebrand disease.
• Platelet transfusion for significant bleeding in inherited disorders or when other measures fail.
• After cardiopulmonary bypass, platelets are damaged by passage through the pump oxygenator — treat post-bypass bleeding with platelet transfusion regardless of the platelet count.
• Flag the diagnosis before any surgery or dental procedure, and plan cover with the haematologist.