Presentation: Thrombocytosis/Thrombocytopenia

Platelet facts: produced by megakaryocytes in the marrow (each megakaryocyte generates roughly 5,000–10,000 platelets); circulate about 7–10 days before removal by the reticuloendothelial system of the spleen and liver. Normal range: 150–450×10⁹/L, with slightly higher counts in women, younger people and Black individuals.

Thrombocytopenia (low platelet count)

• Thrombocytopenia is a platelet count below 150×10⁹/L.
• It is particularly significant if accompanied by other FBC changes, or if the count is falling — a recent decline from a known baseline raises concern.
• Bleeding risk broadly tracks severity: mild (100–150×10⁹/L) is usually asymptomatic, moderate (50–100×10⁹/L) may cause easy bruising, and below 20×10⁹/L spontaneous bleeding becomes common; intracranial bleeding risk rises steeply below 10×10⁹/L.
• Bleeding is unusual at counts above 50×10⁹/L unless there is an associated platelet function defect.

Significant level: < 100×10⁹/L.

Mechanisms and common causes:

• Reduced production: marrow failure (aplastic anaemia), marrow infiltration or displacement (leukaemia, lymphoma, solid-tumour metastases, myelodysplasia), chemotherapy or radiation, chronic alcohol use, folate/vitamin B12/copper deficiency, some viral infections, sepsis.
• Increased destruction — immune: primary immune thrombocytopenia (ITP); drug-induced (heparin, quinine, sulfonamides, vancomycin, and others); secondary to SLE, rheumatoid arthritis, lymphoproliferative disease, or chronic infection (HIV, hepatitis C, Helicobacter pylori); post-transfusion purpura.
• Increased destruction/consumption — non-immune: thrombotic thrombocytopenic purpura (TTP), haemolytic uraemic syndrome, DIC, pre-eclampsia/HELLP, mechanical heart valves.
• Sequestration: hypersplenism — about one-third of the platelet mass normally sits in the spleen, and splenic congestion from cirrhosis pools more.
• Dilutional: massive transfusion or fluid resuscitation; the plasma volume expansion of pregnancy contributes to gestational thrombocytopenia.
• Inherited (usually present in childhood): Fanconi syndrome, thrombocytopenia–absent radius syndrome, Bernard–Soulier syndrome, Wiskott–Aldrich syndrome, May–Hegglin anomaly.

Pseudothrombocytopenia: EDTA-dependent platelet clumping gives a spuriously low automated count — confirm on a film and, if needed, a citrate tube.

Red flags: bruising, petechiae, wet purpura (mucosal — oral blood blisters, gross haematuria), any active bleeding.

• Workup: repeat FBC to exclude lab error, plus blood film and testing for HIV and hepatitis C in isolated thrombocytopenia.
• A falling count with anaemia points to infection, DIC, sepsis, thrombotic microangiopathy or an autoimmune cause; pancytopenia suggests myelodysplasia.
• Add ANA/antiphospholipid antibodies if autoimmune features, PF4 antibodies if there is concurrent thrombosis on heparin, and coagulation studies (PT, aPTT, fibrinogen, LDH) if DIC or a microangiopathy is possible. Check for splenomegaly and lymphadenopathy.
• A bone marrow biopsy is reserved for an unclear cause or suspected primary haematological disorder.

Emergencies

Emergencies needing immediate action: HIT, TTP, HUS, drug-induced ITP, severe thrombocytopenia in pregnancy, and bleeding with severe thrombocytopenia.

Management is directed at the cause — for example plasma exchange for TTP, and immediate withdrawal of all heparin plus a non-heparin anticoagulant for HIT.

Platelet transfusion is for bleeding with severe thrombocytopenia; prophylactic pre-operative transfusion for a low count alone is poorly supported.

Follow-up

Interpret persistently low platelets in context. Consider further testing (blood film, ANA, HIV, HBV/HCV, liver enzymes) and check for splenomegaly/lymphadenopathy on examination.

In one cohort, people with mild thrombocytopenia had about a 12% 10-year probability of developing an autoimmune disorder.

Referral by platelet count:

Platelet count	Referral
< 30×10⁹/L	Requires urgent referral
30–100×10⁹/L	Judgement depending on context — urgent referral if bleeding; further investigation if persistent/progressive; refer if no cause found
100–145×10⁹/L	Follow up counts; investigate if persistent; refer if progressive without an obvious cause

Thrombocytosis (high platelet count)

Thrombocytosis is a platelet count above 450×10⁹/L.

• Around 80–90% of cases are secondary (reactive) — a response to an underlying condition rather than a marrow disorder — driven largely by interleukin-6 raising thrombopoietin and megakaryocyte output.
• Reactive thrombocytosis is generally not associated with increased thrombotic risk and resolves once the cause is treated.
• Reactive causes are often grouped as the “5 I’s”: inflammation, infection, iron deficiency, ischaemia and infarction — plus malignancy, and asplenia (up to ~90% of patients develop thrombocytosis after splenectomy, from loss of splenic pooling; counts can exceed 800×10⁹/L and there is a real thrombotic risk in the first few weeks).
• Drugs (adrenaline, vincristine, all-trans retinoic acid, some antibiotics) and acute exercise cause transient rises.

Significant level: > 500×10⁹/L.

Most likely causes: reactive conditions (infection, inflammation), pregnancy, iron deficiency, post-splenectomy/asplenia, and — uncommonly — essential thrombocythaemia.

When to suspect a primary (clonal) cause: persistence beyond ~6 months, a very high count with no reactive explanation, associated splenomegaly, or a prior thrombosis.

Workup to separate reactive from clonal: blood film, ESR and CRP, iron studies, and — if still unclear — JAK2 V617F, CALR and MPL mutation testing plus BCR-ABL to exclude CML, and occasionally a marrow biopsy.

Essential thrombocythaemia (ET)

Essential thrombocythaemia (ET): a myeloproliferative neoplasm with an isolated persistent platelet count > 450×10⁹/L, megakaryocyte hyperplasia, and a tendency to microvascular symptoms (headache/ocular migraine, paraesthesiae, erythromelalgia, digital ischaemia) and bleeding.

It is a diagnosis of exclusion — reactive causes, polycythaemia vera, CML and myelofibrosis must be excluded.

JAK2 V617F is present in about 50%, CALR in most of the rest, MPL in a few; a JAK2 allele burden > 50% suggests polycythaemia vera or myelofibrosis instead.

There is no correlation between the platelet count and macrovascular thrombosis risk, so platelet-lowering drugs are not used simply to normalise the count in asymptomatic patients.

Low-dose aspirin is the cornerstone for vasomotor symptoms; platelet-lowering therapy (peginterferon, anagrelide, or hydroxyurea) is added for high-risk disease (age > 60 with a JAK2 mutation, or prior thrombosis).

Extreme thrombocytosis (> 1000×10⁹/L) can cause an acquired von Willebrand syndrome and paradoxical bleeding, which is not usually spontaneous.