Presentation: Bruising and Bleeding

See also Presentation: Purpuric Rash for a complementary, purpura-specific diagnostic strategy model.

The three major mechanisms of systemic bleeding disorders:

1. Coagulation deficiencies (reduced/inhibited circulating coagulation factors).
2. Platelet abnormalities (number or function).
3. Vascular defects (of the vascular endothelium).

As with any suspected bleeding disorder, clinical assessment has high sensitivity, although low specificity, for the presence of a bleeding disorder. By contrast, both the sensitivity and specificity of routine laboratory screening are low — both false-negative and false-positive results are common with the basic coagulation “screening tests,” so a directed bleeding history still carries more diagnostic weight than an unselected panel of clotting tests. The commonest cause of an acquired bleeding disorder is drug therapy — aspirin/NSAIDs (platelet dysfunction), cytotoxic drugs (thrombocytopenia), and oral anticoagulants (inhibited vitamin K-dependent factor synthesis) account for most cases seen in general practice.

Von Willebrand disease (vWD) is the most common inherited bleeding disorder. It presents similarly to a platelet abnormality and can exhibit variable clinical symptomatology, ranging from mild mucocutaneous bleeding of the nose or gingiva to menorrhagia to hemarthrosis in more severe cases. Type 1 (a partial quantitative vWF deficiency) accounts for 60–80% of cases and is usually mild; medications that inhibit platelet function (aspirin, NSAIDs) can unmask or worsen symptoms and are often what first triggers the diagnosis being considered. Type 2 subtypes are qualitative vWF defects, and type 3 is a severe, near-total deficiency — desmopressin (DDAVP) is first-line for type 1 but is ineffective in type 2A/3 (no releasable vWF stores to mobilise) and specifically contraindicated in type 2B (risk of provoking thrombocytopenia/thrombosis), so specialist haematology input on subtype is needed before treating a confirmed case, not just a suspected one.

Differential diagnosis

Category	Inherited	Acquired
Vascular disorders	Hereditary haemorrhagic telangiectasia; Marfan syndrome/other connective tissue disorders	Infection (meningococcus, measles, dengue); purpura simplex; senile purpura; Henoch-Schönlein purpura; steroid purpura; vitamin C deficiency (scurvy)
Coagulation factor deficiency/inhibitor	Haemophilia A; haemophilia B; von Willebrand disease	DIC; liver disease; vitamin K deficiency; oral anticoagulant therapy/overdose
Thrombocytopenia	Fanconi syndrome; amegakaryocytic thrombocytopenia	Immune: ITP, drug-induced (e.g. heparin), TTP, post-transfusion purpura. Non-immune: DIC, bone marrow replacement (e.g. leukaemia) or failure, splenic pooling
Functional platelet disorders	Glanzmann thrombasthenia; Bernard-Soulier syndrome; storage pool deficiency	Drug-induced (aspirin, NSAIDs); uraemia/kidney failure; myeloproliferative disorders; dysproteinaemias

History

Factors suggesting a systemic bleeding defect: spontaneous haemorrhage; severe or recurrent haemorrhagic episodes (e.g. epistaxis); bleeding from multiple sites; bleeding out of proportion to trauma; cutaneous or GI bleeding; postpartum haemorrhage; bleeding from tooth extraction/oral cavity; menorrhagia; muscle haematomas or haemarthrosis.

Platelet abnormalities present as early bleeding straight after trauma. Coagulation factor deficiencies present with delayed bleeding, after initial hemostasis by normal platelets has already occurred.

Bleeding history checklist: skin bruising, epistaxis, injury, domestic violence, menorrhagia, haemarthrosis, tooth extraction, unusual haematomas, tonsillectomy/other operations, childbirth, haematuria, rectal bleeding, drugs, family history, comorbidities (liver/kidney disease).

Family history pattern: X-linked recessive → haemophilia A or B; autosomal dominant → vWD, dysfibrinogenaemias; autosomal recessive → deficiency of factors V, VII, X.

Medication history is mandatory. Examples by mechanism:

• Vascular purpura: prednisolone/other steroids.
• Thrombocytopenia: cytotoxic drugs, carbamazepine, gold, sodium valproate, heparin, ranitidine, sulphonamides, quinine/quinidine, thiazide diuretics, penicillins, vancomycin, chloramphenicol.
• Functional platelet abnormalities: aspirin, NSAIDs.
• Coagulation factor deficiency: warfarin.

Examination

Skin: distribution of rash/bruising — Henoch-Schönlein purpura has a classic pattern; senile purpura affects the dorsum of the hands/extensor forearms/shins in the elderly; purpura on the legs suggests platelet disorders, meningococcal septicaemia, or paraproteinaemias; on the fingers/toes suggests vasculitis.

Lips and oral mucosa: telangiectasia (hereditary haemorrhagic telangiectasia); gum hypertrophy (monocytic leukaemia). Lymphadenopathy and splenomegaly. Ocular fundi: retinal haemorrhages. Urinalysis: for micro/macroscopic blood.

Investigations

• FBC and platelet morphology give aetiological clues (e.g. thalassaemia, sickle cell).
• Coagulation defect suspected: PT/INR, APTT, fibrinogen level, thrombin time (TT).
• Platelet pathology suspected: platelet count, skin bleeding time (of doubtful value), platelet function analyser (PFA-100).
• Inherited disorder suspected (specialist-ordered): factor VIII, vWF activity, vWF antigen.
• Other: ESR/CRP, autoimmune screen, kidney function, LFTs, plasma electrophoresis, skin biopsy.

Why the skin bleeding time is of doubtful value: it should not be performed if the platelet count is <100 x 10⁹/L and if the patient has taken aspirin in the preceding 7-10 days, or a NSAID in the past 1-4 days, and even when technically valid it is prone to inter-operator and inter-laboratory variability, so “the test cannot be recommended as a predictor of surgical bleeding.” It has essentially been superseded by directed history plus platelet count/function testing.

Interpreting APTT and PT in practice: the APTT’s main clinical uses are monitoring full dose, continuous infusion heparin therapy and the detection of significant coagulation factor deficiencies in patients with a history suggestive of an inherited bleeding disorder” — in a patient with no such history, “the yield from the APTT is very low,” and it “has little or no value when used as a ‘routine’ preoperative screening test.” The PT/INR’s main uses are monitoring oral anticoagulant therapy and assessing hepatocellular disease/vitamin K status; like the APTT, it “has only a limited role in the assessment of patients with a history suggestive of an inherited bleeding disorder when ordered as an unselected screening test.

Blood changes by specific coagulation factor disorder:

	Haemophilia A	vWD	Vitamin K deficiency
PT	Normal	Normal	↑
APTT	↑	↑	↑
TT	Normal	Normal	Normal