Platelet Disorders

Introduction

Platelets provide primary haemostasis - adhering to damaged endothelium, activating, and aggregating to form the initial platelet plug that is subsequently stabilised by the fibrin mesh of the coagulation cascade. Disorders of platelet number or function therefore impair the body's immediate response to vascular injury.¹

This article takes a structured approach to the abnormal platelet count, which is one of the commonest abnormalities encountered on a full blood count. Two conditions in this group - immune thrombocytopenic purpura and disseminated intravascular coagulation - are covered in their own articles, and are referred to here only in the context of the wider differential.

Recognising a platelet problem clinically

The pattern of bleeding is one of the most useful pieces of clinical information in haematology, because it separates platelet (primary haemostatic) disorders from coagulation factor (secondary haemostatic) disorders before any test is sent.

Thrombocytopenia

Defined as a platelet count below 150 x10^9/L. The first and most important step is to confirm it is genuine.

Step one: exclude pseudothrombocytopenia

EDTA (the standard FBC anticoagulant) can cause platelets to clump in vitro in some individuals, which the analyser counts as a single platelet, producing a falsely low result in a completely well patient. It is confirmed by finding platelet clumps on the blood film, and resolved by repeating the sample in a citrate tube. Failing to exclude this leads to unnecessary investigation and, occasionally, to inappropriate treatment.

Step two: classify by mechanism

Assessing bleeding risk

Heparin-induced thrombocytopenia

HIT deserves separate attention because it behaves in the opposite way to every other cause of thrombocytopenia: it causes thrombosis, not bleeding, and the correct treatment is more anticoagulation, not less.²

Mechanism: antibodies form against complexes of heparin and platelet factor 4 (PF4). These immune complexes bind and activate platelets, causing simultaneous platelet consumption (hence the falling count) and widespread platelet activation, generating thrombin and driving arterial and venous thrombosis.

• Timing: platelet count falls typically 5-10 days after starting heparin (sooner with recent prior exposure), with a fall of more than 30-50% from baseline
• More common with unfractionated heparin than low molecular weight heparin
• Assessment: the 4Ts score (Thrombocytopenia degree, Timing, Thrombosis, oTher causes) estimates probability and guides testing; confirm with anti-PF4/heparin antibody assays and functional testing
• Management: stop all heparin immediately (including flushes and heparin-bonded lines) and start a non-heparin anticoagulant (e.g. argatroban, danaparoid, or fondaparinux per local policy)
• Do not give platelet transfusions routinely - they may fuel further thrombosis; and do not start warfarin alone while the platelet count is low, given the risk of venous limb gangrene and skin necrosis

Thrombocytosis

Defined as a platelet count above 450 x10^9/L. The key distinction is between a reactive rise (far commoner) and a clonal marrow disorder.

An important practical point: reactive thrombocytosis does not require treatment aimed at the platelet count, however high it is. Investigating and treating the underlying cause is what matters - a very high platelet count in a patient with sepsis or newly diagnosed iron deficiency is an expected finding, not an indication for aspirin.

Disorders of platelet function

These cause bleeding with a normal platelet count, and are easily missed if the FBC alone is used to assess haemostasis.

Acquired (much commoner)

• Aspirin - irreversibly inhibits cyclo-oxygenase-1, blocking thromboxane A2 production; the effect lasts the lifetime of the platelet (7-10 days), since platelets have no nucleus and cannot regenerate the enzyme
• Clopidogrel, ticagrelor and prasugrel - block the platelet P2Y12 ADP receptor
• NSAIDs - reversible COX inhibition, so a shorter-lived effect than aspirin
• Uraemia - chronic kidney disease impairs platelet function through retained uraemic toxins; may respond to desmopressin (DDAVP) or dialysis
• Liver disease, myeloproliferative neoplasms (very high counts can cause an acquired von Willebrand-like defect), and cardiopulmonary bypass

Inherited (rare)

• Glanzmann thrombasthenia - deficiency of GPIIb/IIIa, so platelets cannot aggregate with each other via fibrinogen
• Bernard-Soulier syndrome - deficiency of GPIb, so platelets cannot adhere to von Willebrand factor at the vessel wall; characteristically with large platelets and mild thrombocytopenia
• Storage pool disorders - deficient platelet granule contents

Investigations

• FBC - defines the count and shows whether other cell lines are involved (pointing towards a marrow process or hypersplenism)
• Blood film - essential in every case: excludes platelet clumping, and looks for schistocytes (TTP/HUS/DIC), blasts (leukaemia), large platelets (Bernard-Soulier, myeloproliferative disease, ITP) and dysplastic features (MDS)
• Coagulation screen (PT, APTT, fibrinogen) - normal in ITP; deranged with low fibrinogen and raised D-dimer in DIC
• U&Es, LFTs - renal impairment (HUS, uraemic platelet dysfunction), liver disease with hypersplenism
• Haemolysis screen (LDH, bilirubin, haptoglobin, reticulocytes) if a microangiopathic process is suspected
• B12, folate, ferritin - deficiency states cause thrombocytopenia; iron deficiency causes reactive thrombocytosis
• Virology (HIV, hepatitis C) and autoimmune screen where secondary immune thrombocytopenia is possible
• Anti-PF4/heparin antibodies if HIT is suspected, alongside a 4Ts score
• JAK2/CALR/MPL testing for suspected clonal thrombocytosis
• Bone marrow biopsy - reserved for unexplained cytopenias, atypical features, or suspected marrow pathology, rather than performed routinely

Management principles

• Treat the underlying cause - this is definitive management for the great majority of platelet disorders, whether that is stopping a drug, correcting B12 deficiency, treating sepsis or managing liver disease
• Stop or review contributing drugs - antiplatelet agents, heparin (mandatory in HIT), and other implicated medications
• Platelet transfusion for active significant bleeding, or prophylactically in marrow failure at counts below around 10 x10^9/L, or to cover invasive procedures at locally agreed thresholds. It is contraindicated or of no value in TTP and HIT, where it may worsen thrombosis, and is largely ineffective in ITP outside emergencies because transfused platelets are destroyed as fast as the patient's own
• Tranexamic acid is a useful adjunct for mucosal bleeding and menorrhagia, though it is generally avoided in haematuria given the risk of clot retention
• Desmopressin (DDAVP) for uraemic platelet dysfunction
• Disease-specific treatment - corticosteroids/IVIG for ITP, plasma exchange for TTP, non-heparin anticoagulation for HIT, cytoreduction for clonal thrombocytosis

Red flags

Prognosis

Prognosis is determined almost entirely by the underlying cause rather than by the platelet count itself. Reactive thrombocytosis and drug-induced platelet dysfunction resolve completely once the trigger is removed or treated. Gestational thrombocytopenia resolves after delivery. Pseudothrombocytopenia requires no treatment at all.

At the other end of the spectrum, TTP, HIT and DIC carry significant mortality if not recognised and treated promptly and correctly - and in each case the harm often comes from applying the standard reflex (transfuse platelets, stop anticoagulation) rather than the condition-specific one.² Thrombocytopenia arising from marrow failure or infiltration carries the prognosis of the underlying haematological disease.