Thrombocytopenia

Thrombocytopenia is a platelet count under 150 x 10^9/L. Bleeding risk depends on the count and cause: spontaneous bleeding is unusual above 30 x 10^9/L and serious bleeding is rare above 50 x 10^9/L unless there is a platelet function defect or other haemostatic problem.

• Reduced production: aplastic anaemia, myelodysplasia, leukaemia, marrow infiltration, B12 and folate deficiency, alcohol, viral infections (HIV, hepatitis C, EBV, parvovirus), chemotherapy and radiotherapy, congenital thrombocytopenias.
• Increased destruction (immune): immune thrombocytopenia (primary or secondary to HIV, hepatitis C, H. pylori, lupus, antiphospholipid syndrome, lymphoproliferative disease, drugs, vaccination), drug induced (heparin, quinine, linezolid, vancomycin, carbamazepine, valproate, trimethoprim-sulfamethoxazole, beta lactams), post-transfusion purpura.
• Consumption: disseminated intravascular coagulation, thrombotic microangiopathies (thrombotic thrombocytopenic purpura, haemolytic uraemic syndrome, pre-eclampsia with HELLP syndrome), dengue, malaria, sepsis, snakebite coagulopathy, mechanical valves.
• Sequestration: hypersplenism (cirrhosis, portal hypertension, malaria, schistosomiasis, myelofibrosis).
• Dilutional: massive transfusion.
• Spurious: EDTA-induced platelet clumping and giant platelets, corrected by repeat sampling in citrate or heparin.
• Gestational thrombocytopenia: mild (usually over 70 x 10^9/L), late pregnancy, benign.

• Mucocutaneous bleeding: petechiae (non-blanching pinpoint spots on legs and pressure areas), purpura, easy bruising, gum bleeding, nosebleeds, heavy periods, gastrointestinal and urinary bleeding; wet purpura (blood blisters in the mouth) predicts serious bleeding.
• Severe cases: intracranial haemorrhage (headache, vomiting, neurological signs), retinal haemorrhage.
• Clues to the cause: fever, confusion, renal failure and haemolysis (thrombotic thrombocytopenic purpura); recent drugs or heparin exposure; infections, travel and sick contacts; weight loss and night sweats; liver disease and splenomegaly; alcohol; pregnancy; family history.
• Examination: skin, mucosa, spleen, liver, lymph nodes, signs of chronic liver disease, signs of sepsis, and neurological examination.
• Red flags: platelets under 20 x 10^9/L with bleeding, under 10 without bleeding, neurological symptoms, fever, haemolytic anaemia, renal impairment, pregnancy, or anticoagulant use.

• Repeat the FBC and examine the blood film: clumping, giant platelets, schistocytes (microangiopathy), blasts, dysplastic neutrophils, leucoerythroblastic changes, parasites.
• Tests: reticulocytes, lactate dehydrogenase, bilirubin, haptoglobin, direct antiglobulin test, creatinine, liver function, clotting profile, fibrinogen and D-dimer (DIC), B12, folate, thyroid function, antinuclear antibodies, antiphospholipid antibodies, HIV, hepatitis B and C, H. pylori (stool antigen or breath test), immunoglobulins, and pregnancy test.
• Dengue NS1 antigen, malaria film.
• Abdominal ultrasound for spleen and liver.
• Bone marrow aspirate and biopsy for age over 60, atypical features, other cytopenias, or no response to initial treatment of suspected immune thrombocytopenia.
• ADAMTS13 activity (thrombotic thrombocytopenic purpura; PLASMIC score), heparin induced thrombocytopenia testing (4Ts score, PF4 antibodies).
• Immune thrombocytopenia is a diagnosis of exclusion with isolated thrombocytopenia, a normal film, and no other cause.

Emergencies

• Thrombotic thrombocytopenic purpura (thrombocytopenia with microangiopathic haemolysis, fever, renal or neurological signs): same day plasma exchange (1.5 plasma volumes daily), prednisolone 1 mg/kg, caplacizumab 10 mg intravenously then daily subcutaneously, and rituximab 375 mg/m2; avoid platelet transfusion unless life threatening bleeding.
• Heparin induced thrombocytopenia (fall of over 50 percent 5 to 10 days after heparin start): stop all heparin, start a non-heparin anticoagulant (argatroban 2 micrograms/kg/min or fondaparinux 7.5 mg daily), and avoid warfarin until platelets recover.
• DIC: treat the cause; platelets for bleeding; fresh frozen plasma 15 mL/kg and cryoprecipitate if fibrinogen is under 1.5 g/L with bleeding.
• Life threatening bleeding: platelet transfusion (one adult dose), tranexamic acid 1 g intravenously over 10 minutes then 1 g over 8 hours, and treatment of the cause.

Primary immune thrombocytopenia (adults)

• Observation without treatment if platelets are over 30 x 10^9/L, no bleeding, and no risk factors.
• First line when treatment is needed (platelets under 30, bleeding, procedures): prednisolone 1 mg/kg orally daily (maximum 80 mg) for 2 to 3 weeks then taper, or dexamethasone 40 mg orally daily for 4 days (repeat every 14 to 28 days for up to 3 cycles); intravenous immunoglobulin 1 g/kg for 1 to 2 days when a fast rise is needed.
• Second line: thrombopoietin receptor agonists (eltrombopag 25 to 75 mg daily on an empty stomach, romiplostim 1 to 10 micrograms/kg weekly), rituximab 375 mg/m2 weekly for 4 doses, fostamatinib, or splenectomy (after 12 months).
• Treat H. pylori if positive (omeprazole 20 mg, amoxicillin 1 g and clarithromycin 500 mg twice daily for 14 days); treat hepatitis C and HIV.
• Avoid NSAIDs, aspirin, intramuscular injections, and contact sports if platelets are under 50 x 10^9/L.
• Platelet thresholds for procedures: over 50 for major surgery and lumbar puncture, over 20 for central line insertion, over 10 for most minor procedures.

Other causes

• Drug induced: stop the drug; recovery in 5 to 10 days.
• Hypersplenism: treat the cause; splenectomy or embolisation rarely.
• Megaloblastic anaemia and alcohol: replace B12 and folate, stop alcohol.
• Malaria and dengue: specific treatment, careful fluid management, and platelet transfusion only for significant bleeding.
• Gestational thrombocytopenia: observe; check for pre-eclampsia and HELLP syndrome.

Follow up

• Repeat FBC within 24 to 48 hours for counts under 50, weekly while treatment is changing, and every 3 to 6 months when stable; refer to haematology for counts under 30, persistent unexplained thrombocytopenia, or suspected malignancy.

Special groups

• Pregnancy: immune thrombocytopenia treated with prednisolone 10 to 20 mg daily or intravenous immunoglobulin when counts are under 30 or bleeding; avoid rituximab and thrombopoietin agents unless specialist; epidural anaesthesia if platelets exceed 70 x 10^9/L; thrombotic thrombocytopenic purpura and HELLP need urgent obstetric and haematology care.
• Children: acute immune thrombocytopenia often resolves in 6 months; observation for mild bleeding; prednisolone 1 to 2 mg/kg daily for 5 to 7 days, or intravenous immunoglobulin 0.8 to 1 g/kg once for significant bleeding.