Vascular and Platelet Function Disorders

Overview

Bleeding can also come from bad vessel-wall support (vascular purpuras) or normal-number-but-dysfunctional platelets (platelet function disorders). Both: normal platelet count, usually normal coag screen, but prolonged bleeding time + skin/mucosal bleeding.

Vascular purpuras (non-thrombocytopenic)

Mild, skin/mucosa-confined (petechiae, purpura, ecchymoses). From endothelial damage, subendothelial matrix defect, or abnormal vessel formation.

Inherited:

Hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu) — AD, dilated capillaries (lips, tongue, nose, palms/soles), GI/mucosal bleeding
Connective tissue disorders — Marfan, Ehlers-Danlos, pseudoxanthoma elasticum — fragile vessels

Acquired:

Henoch-Schönlein purpura — self-limited hypersensitivity vasculitis, children/young adults. Purpuric rash (extensor arms/legs/buttocks) + haematuria + colicky abdominal pain + polyarthralgia + acute nephritis. Coag tests NORMAL. Leucocytoclastic vasculitis; IgA+C3+fibrin immune complex deposition (± properdin → alternate complement pathway)
Haemolytic-uraemic syndrome — infancy/early childhood, bleeding + renal failure, glomerular hyaline microthrombi
Simple easy bruising — women, childbearing age, unexplained
Infection (septicaemia, severe measles) — endothelial toxicity or DIC
Drug reactions — hypersensitivity vasculitis
Steroid purpura, senile purpura, scurvy (defective collagen → vessel fragility)

Platelet function disorders

Prolonged bleeding time + NORMAL platelet count. Hereditary or acquired.

Hereditary — grouped by which step fails:

Adhesion defect — Bernard-Soulier syndrome (AR, missing platelet membrane glycoprotein needed for vessel-wall adhesion); vWD also causes this
Aggregation defect — Glanzmann’s thrombasthenia (fails ADP/collagen-induced aggregation, GpIIb-IIIa defect)
Release reaction defect — normal initial aggregation but defective ADP/prostaglandin/5-HT release (storage pool-type)

Acquired:

Aspirin — inhibits COX → ↓prostaglandin → impaired aggregation+release; same mechanism used clinically to prevent thromboembolism/recurrent MI
Others: uraemia, liver disease, myeloma, Waldenström’s, myeloproliferative disorders

Clinical relevance

Normal platelet count + prolonged bleeding time + mucocutaneous bleeding = signature pointing away from thrombocytopenia and coagulation-factor disorders, toward vascular/platelet-function cause. Bernard-Soulier (adhesion) vs Glanzmann’s (aggregation) — easy to confuse, distinguish by which step of primary haemostasis fails. Aspirin’s bleeding side-effect and its cardioprotective benefit are the same COX-inhibition mechanism. HSP’s tetrad with normal coag tests is a classic pattern — looks like bleeding disorder, is actually immune-complex vasculitis.

Overview

Beyond thrombocytopenia (reduced platelet number), bleeding can also arise from defective vessel-wall support (vascular purpuras) or from platelets present in normal numbers but functioning abnormally (platelet function disorders). Both groups characteristically show a normal platelet count, and most standard coagulation screening tests are normal too — the diagnostic clue is a prolonged bleeding time with skin/mucosal bleeding rather than deep tissue haemorrhage.

Vascular Bleeding Disorders (Purpuras)

Also called non-thrombocytopenic purpuras. Bleeding is usually mild, confined to skin and mucous membranes (petechiae, purpura, ecchymoses), and arises from damage to capillary endothelium, subendothelial matrix abnormalities, or abnormal vessel formation. Standard haemostasis screening (bleeding time, coagulation time, platelet count/function) is typically normal, which is why the pathogenesis is often poorly demonstrated on routine workup.

Inherited

Hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu disease) — autosomal dominant, childhood onset; telangiectatic (dilated) capillaries from vascular malformation, especially on lips, tongue, nose, palms, soles. Presents with GI bleeding, epistaxis, other mucosal bleeding.
Inherited connective tissue matrix disorders — Marfan syndrome, Ehlers-Danlos syndrome, pseudoxanthoma elasticum; fragile skin vessels, easy bruising.

Acquired

Henoch-Schönlein purpura — a self-limited hypersensitivity vasculitis of children and young adults. Produces purpuric rash over extensor surfaces of arms/legs/buttocks, plus haematuria, colicky abdominal pain (GIT bleeding), polyarthralgia, and acute nephritis — despite these haemorrhagic features, coagulation tests are normal. Vessel wall shows leucocytoclastic vasculitis (viable and necrotic neutrophils); circulating immune complexes of IgA, C3, and fibrin (sometimes properdin, suggesting alternate complement pathway activation) deposit in the vessel wall.
Haemolytic-uraemic syndrome — disease of infancy/early childhood; bleeding tendency with variable acute renal failure; confined pathologically to the kidney, with hyaline microthrombi in glomerular capillaries.
Simple easy bruising (“Devil’s pinches”) — common, unexplained, in women of childbearing age.
Infection — septicaemia and severe measles particularly, via toxic endothelial damage or DIC.
Drug reactions — certain drugs trigger hypersensitivity (leucocytoclastic) vasculitis.
Steroid purpura — long-term steroid therapy or Cushing syndrome, from defective vascular support.
Senile purpura — atrophy of supportive tissue around cutaneous vessels in old age, especially dorsum of forearm/hand.
Scurvy — vitamin C deficiency causes defective collagen synthesis, producing skin, muscle, and occasionally GI/genitourinary bleeding.

Disorders of Platelet Function

Suspected when there is skin/mucosal haemorrhage with a prolonged bleeding time but normal platelet count. May be hereditary or acquired.

Hereditary — Grouped by the Functional Step Affected

Defective platelet adhesion
- Bernard-Soulier syndrome — autosomal recessive; inherited deficiency of a platelet membrane glycoprotein essential for platelet adhesion to the vessel wall.
- Von Willebrand disease — also produces defective adhesion, alongside its factor VIII deficiency (see Von Willebrand Disease).
Defective platelet aggregation
- Glanzmann’s thrombasthenia — failure of primary platelet aggregation with ADP or collagen, from an inherited defect (deficiency of the GpIIb-IIIa complex needed for fibrinogen-bridged aggregation).
Disorders of platelet release reaction
- Normal initial aggregation with ADP or collagen, but subsequent release of ADP, prostaglandins, and 5-HT is defective due to complex intrinsic (granule) deficiencies — storage pool-type defects.

Acquired

Aspirin therapy — prolonged use causes easy bruising and abnormal bleeding time; aspirin inhibits cyclooxygenase, suppressing prostaglandin synthesis needed for platelet aggregation and the release reaction. This same anti-platelet effect is exploited clinically to prevent thromboembolic disease and recurrent myocardial infarction.
Others — uraemia, liver disease, multiple myeloma, Waldenström’s macroglobulinaemia, and various myeloproliferative disorders can each impair platelet function at different levels.

Clinical Relevance

The shared diagnostic signature — normal platelet count, prolonged bleeding time, mucocutaneous (not deep-tissue) bleeding — is what separates this entire group from both thrombocytopenic disorders (low count) and coagulation factor disorders (deep muscle/joint bleeding); recognising this pattern is what should direct a workup toward vascular or platelet-function causes rather than a platelet-count or coagulation-factor problem.
Bernard-Soulier syndrome (adhesion defect) and Glanzmann’s thrombasthenia (aggregation defect) are frequently confused because both are inherited, autosomal, and produce a bleeding tendency with normal platelet count — the distinguishing point is which step of primary haemostasis fails: adhesion to the vessel wall (Bernard-Soulier) versus platelet-platelet aggregation (Glanzmann’s).
Aspirin’s mechanism (irreversible cyclooxygenase inhibition, blocking prostaglandin-dependent aggregation/release) is the same mechanism exploited therapeutically for cardiovascular prophylaxis — the “bleeding side effect” and the “clinical benefit” are two faces of the identical pharmacological action.
Henoch-Schönlein purpura’s tetrad (purpuric rash, abdominal pain, arthralgia, nephritis) with entirely normal coagulation tests is a classic exam pattern precisely because it looks like a bleeding disorder clinically while being, mechanistically, an immune-complex vasculitis rather than a defect of haemostasis at all.

No Rendered Diagram for This Topic

This topic is a classification of causes (vascular purpuras: inherited vs acquired; platelet function disorders: adhesion vs aggregation vs release-reaction defects) rather than a single multi-step mechanism — a rendered process diagram would not add clarity beyond the grouped lists already in notes.md.

Hand-Draw Suggestion

Draw the three-step primary-haemostasis chain (platelet adhesion → aggregation → release reaction) as a simple arrow diagram, and tag each step with the disorder that blocks it: Bernard-Soulier (adhesion), Glanzmann’s thrombasthenia (aggregation), storage pool-type defects (release). This single picture ties the whole hereditary platelet-function section together for quick recall.