Screen for severe thrombocytopenia, active bleeding, thrombotic microangiopathy (TTP/HUS), and DIC. These require emergency or same-day haematology.
Platelets <10 × 10⁹/L carry 20% risk of spontaneous intracranial haemorrhage (ICH). Mortality from ICH is 50%. Same-day platelet transfusion and IVIg/steroids can raise platelets to safe levels within 24-48 hours.
TTP (thrombotic thrombocytopenic purpura) is a haematological emergency. Untreated mortality is 90%. Plasma exchange (plasmapheresis) started within 24 hours reduces mortality to <10%. Classic pentad: fever, MAHA, AKI, thrombocytopenia, neuro symptoms (present in only 40% of cases).
HELLP syndrome (Haemolysis, Elevated Liver enzymes, Low Platelets) complicates 0.5-0.9% of pregnancies. Presents with epigastric pain, nausea, headache. Maternal mortality 1%, fetal mortality 10-60%. Requires emergency delivery.
DIC (disseminated intravascular coagulation) consumes platelets and clotting factors. Triggered by sepsis, trauma, obstetric catastrophe, malignancy. Prolonged APTT/PT, low fibrinogen, raised D-dimer. Treat underlying cause (sepsis source control, delivery in AFLP).
Confirm true thrombocytopenia and exclude lab artifact (pseudothrombocytopenia). A single low platelet count may be spurious due to clumping.
Pseudothrombocytopenia is a lab artifact in 0.1% of samples. EDTA (anticoagulant in FBC tubes) causes platelet clumping in some patients. Automated counters undercount platelets. Blood film shows normal platelet count with clumps visible. Citrate sample corrects the count. No treatment needed.
Blood film review is essential for all platelets <100 × 10⁹/L. It can diagnose TTP (schistocytes), ITP (large young platelets), MDS (dysplastic cells), and exclude pseudothrombocytopenia (platelet clumps). Automated counters miss morphological clues in 10-15% of cases.
Bleeding threshold: Platelets >50 × 10⁹/L rarely cause spontaneous bleeding. Surgical haemostasis is safe down to 50. Platelets 20-50 cause easy bruising but not major bleeding. Platelets 10-20 cause petechiae and mucosal bleeding. Platelets <10 carry 20% risk of spontaneous ICH within weeks.
Transient thrombocytopenia post-viral infection (EBV, dengue, COVID) is common. Platelets can drop to 50-100 × 10⁹/L but recover within 2-4 weeks. Repeating FBC avoids unnecessary haematology referral and anxiety.
Classify thrombocytopenia by severity, mechanism (decreased production vs increased destruction), and whether other cell lines are affected.
Bleeding risk stratification guides urgency. Platelets >50 × 10⁹/L are safe for surgery and daily life. Platelets 20-50 cause easy bruising but rarely major bleeding. Platelets 10-20 require caution (avoid contact sports, NSAIDs). Platelets <10 require admission for bleeding risk monitoring.
Isolated thrombocytopenia (normal Hb/WCC) suggests peripheral destruction (ITP, TTP, drug-induced) rather than bone marrow failure. The marrow is producing platelets normally, but they're being destroyed in the spleen or by antibodies. Prognosis is better than pancytopenia.
Pancytopenia (low platelets + Hb + WCC) indicates bone marrow failure or infiltration. Urgent bone marrow biopsy differentiates aplastic anaemia (empty marrow, treat with immunosuppression), MDS (dysplastic marrow, supportive care ± chemotherapy), and acute leukaemia (blast infiltration, immediate chemotherapy).
Gestational thrombocytopenia affects 5-10% of pregnancies. Platelets drop to 100-150 × 10⁹/L in third trimester. Benign, resolves postpartum. No treatment needed unless <70 (consider ITP). Distinguish from HELLP/pre-eclampsia (these have hypertension, proteinuria, symptoms).
Examine for signs of bleeding, organomegaly, and underlying conditions causing thrombocytopenia.
Petechiae vs purpura vs ecchymoses: Petechiae (pinpoint, 1-2 mm) indicate severe thrombocytopenia (<20 × 10⁹/L). Purpura (3 mm-1 cm) occur at platelets 20-50. Ecchymoses (large bruises >1 cm) occur with minor trauma at platelets <50. Location matters: petechiae on legs/feet (gravity-dependent) are less concerning than trunk/face.
Splenomegaly in thrombocytopenia suggests splenic sequestration (hypersplenism) or lymphoproliferative disease. In ITP, the spleen is normal size or mildly enlarged (1-2 cm). Massive splenomegaly (>8 cm) points to CML, lymphoma, or myelofibrosis, not isolated ITP.
Hepatosplenomegaly with thrombocytopenia suggests chronic liver disease. Portal hypertension causes splenomegaly (congestive) and hypersplenism (splenic sequestration of platelets). Platelets are typically 50-100 × 10⁹/L in cirrhosis, rarely <50 unless decompensated.
Fundoscopy is essential if platelets <20 × 10⁹/L. Retinal haemorrhages indicate high bleeding risk and may predict ICH. If retinal bleeds are present, admit for platelet transfusion even if asymptomatic otherwise.
Investigate based on severity, clinical context, and blood film findings. Target investigations to the likely differential diagnosis.
Blood film is mandatory for all platelets <100 × 10⁹/L. It differentiates ITP (large young platelets), TTP (schistocytes >1%), MDS (dysplastic cells), and pseudothrombocytopenia (platelet clumps). Without a blood film, you cannot confidently diagnose ITP.
Clotting screen differentiates isolated thrombocytopenia (ITP, normal PT/APTT) from DIC (prolonged PT/APTT, low fibrinogen) and liver disease (prolonged PT, normal APTT). In ITP, clotting is normal because clotting factors are unaffected; only platelet number is low.
TTP diagnosis: Pentad is present in only 40%. Require: thrombocytopenia + MAHA (schistocytes, LDH >1000, low haptoglobin, negative Coombs). ADAMTS13 <10% confirms TTP. Plasma exchange must start empirically before ADAMTS13 results (takes 48-72 hours); delaying kills patients.
ITP is a diagnosis of exclusion. Must rule out HIV, HCV, SLE, drugs, TTP, MDS. If isolated thrombocytopenia with normal blood film (apart from large platelets) and no secondary cause, ITP is presumed. Bone marrow biopsy not needed unless atypical features (age >60, systemic symptoms, cytopenia).
Refer based on severity, bleeding risk, mechanism, and pregnancy status. Severe thrombocytopenia requires same-day haematology.
Platelets <10 × 10⁹/L require same-day referral even if asymptomatic. ICH risk is 20% within weeks. IVIg (1 g/kg for 1-2 days) raises platelets to >50 × 10⁹/L within 24-48 hours in 80% of ITP cases, preventing ICH. Prednisolone 1 mg/kg also works but takes 3-7 days.
TTP requires emergency plasma exchange. Untreated mortality is 90%. Plasma exchange reduces mortality to <10% if started within 24 hours. Cannot wait for ADAMTS13 results (take 48-72 hours). If pentad suspected, activate haematology immediately for apheresis machine.
HIT (heparin-induced thrombocytopenia) occurs in 1-5% of heparin recipients, typically day 5-14. Paradoxically causes thrombosis (30-50% risk) despite low platelets. Stop all heparin (including flushes). Start alternative anticoagulation (fondaparinux, argatroban). Same-day haematology for HIT antibody testing.
Gestational thrombocytopenia is benign if platelets >70 × 10⁹/L and no symptoms. Below 70, consider ITP (requires steroids/IVIg before delivery). Epidural analgesia is unsafe if platelets <80; plan alternative analgesia or C-section under GA.
Treatment depends on cause and severity. Primary care can manage mild asymptomatic ITP; severe cases require haematology input for IVIg, steroids, or platelet transfusion.
ITP treatment ladder (haematology-managed):
ITP platelets >30 × 10⁹/L do not require treatment if asymptomatic. Spontaneous remission occurs in 30% within 6 months. Treatment (steroids, IVIg) has side effects and only temporarily raises platelets in most patients. Watchful waiting is safe as long as no bleeding and patient avoids high-risk activities.
IVIg mechanism: Saturates Fc receptors on splenic macrophages, preventing antibody-coated platelet destruction. Works within 24-48 hours in 80% of patients. Expensive (£1000-2000 per dose). Used for urgent platelet rise (pre-surgery, active bleeding) or when steroids contraindicated (diabetes, psychosis).
Prednisolone suppresses autoantibody production. Response takes 3-7 days. 70-80% respond initially, but relapse is common on tapering (50% relapse rate). Long-term steroids are avoided due to osteoporosis, diabetes, weight gain, immunosuppression. Taper over 8 weeks after platelet count >100 × 10⁹/L.
Platelet transfusion in ITP is largely futile unless life-threatening bleeding (ICH, major GI bleed). Transfused platelets are destroyed by the same antibodies within hours. IVIg + steroids + transfusion together may buy time (IVIg blocks antibodies transiently, allowing transfused platelets to survive longer).
Lifestyle modifications reduce bleeding risk in patients with chronic thrombocytopenia. Education on recognizing serious bleeding is critical.
NSAIDs (aspirin, ibuprofen, naproxen) irreversibly inhibit COX-1, impairing platelet function for 7-10 days. In thrombocytopenia, this doubles bleeding risk. Even single-dose aspirin causes measurable prolongation of bleeding time. Paracetamol is safe (no antiplatelet effect).
Contact sports risk head trauma. ICH is the leading cause of death in severe thrombocytopenia (<10 × 10⁹/L). Even minor head knocks can cause subdural haematoma if platelets <50 × 10⁹/L. Swimming, walking, yoga are safe alternatives.
Heavy menstrual bleeding (menorrhagia) affects 80% of women with platelets <50 × 10⁹/L. Tranexamic acid (antifibrinolytic) reduces bleeding by 40-50% during menses. Mirena coil (levonorgestrel IUS) reduces bleeding by 90% and is first-line for chronic ITP in women of reproductive age.
Recognizing ICH early saves lives. Sudden severe headache, vomiting, confusion, focal weakness, seizures are red flags. ICH mortality is 50% even with treatment. Platelets <10 × 10⁹/L carry 20% ICH risk within weeks; patient education on warning signs is mandatory.
Monitor platelet trajectory, watch for bleeding, and re-refer if platelets falling or new symptoms. Chronic thrombocytopenia requires long-term surveillance.
Platelet trajectory predicts prognosis in ITP. Steadily rising platelets (30 → 50 → 80 over 3 months) suggest spontaneous remission. Platelets fluctuating wildly (50 → 20 → 60 → 10) suggest chronic relapsing ITP requiring long-term treatment. Platelets persistently <20 despite treatment warrant escalation to rituximab or TPO agonists.
Spontaneous remission occurs in 30% of ITP cases within 6 months, especially in children and young adults post-viral infection. Median time to remission is 3 months. This is why watch-and-wait is acceptable for platelets >30 × 10⁹/L with no bleeding.
ICH risk is the primary concern in severe thrombocytopenia. Incidence is 1-2% per year at platelets 10-20 × 10⁹/L, rising to 5-10% per year at platelets <10 × 10⁹/L. Sudden severe headache in a thrombocytopenic patient is ICH until proven otherwise; CT head within 1 hour is mandatory.
Chronic ITP (platelets <100 × 10⁹/L for >12 months) requires long-term haematology follow-up. 50% relapse after stopping treatment. Second-line therapies (rituximab, TPO agonists, splenectomy) have different risk-benefit profiles; shared decision-making with patient and haematologist is essential.