Thrombocytopaenia

Thrombocytopaenia is a platelet count below 150 × 10⁹/L. The count alone is a poor guide to risk, and the useful thresholds are these: spontaneous bleeding is uncommon above 50, surgery is generally safe above 50, and the risk of serious spontaneous haemorrhage rises sharply below 20 and particularly below 10.

There are only three mechanisms, and identifying which one is operating is the whole of the diagnostic approach.

Reduced Production

Marrow failure or suppression. Aplastic anemia; leukaemia, lymphoma or metastatic marrow infiltration; myelodysplastic syndrome; chemotherapy and radiotherapy; deficiency of vitamin B12 or folate; alcohol, which suppresses megakaryocytes directly; and viral infection including HIV, hepatitis C, EBV and parvovirus.

Increased Destruction

The commonest group.

• Immune thrombocytopenia (ITP) — autoantibodies against platelet glycoproteins. Acute post-viral ITP in children usually resolves spontaneously; adult ITP tends to be chronic.
• Heparin-induced thrombocytopenia (HIT) — antibodies to the heparin-platelet factor 4 complex, developing 5–10 days after exposure. It is a prothrombotic state despite the low count, and this is the critical point: the danger is clot, not bleeding, and platelet transfusion is contraindicated.
• Thrombotic microangiopathies — thrombotic thrombocytopenic purpura (TTP), from deficient ADAMTS13 activity, and haemolytic uremic syndrome. Both consume platelets in microthrombi.
• Disseminated intravascular coagulation (DIC) — widespread activation of coagulation consuming platelets and clotting factors.
• Drug-induced immune thrombocytopenia — quinine and quinidine are classic; also sulfonamides, vancomycin, rifampicin, carbamazepine and glycoprotein IIb/IIIa inhibitors.
• Autoimmune disease, particularly SLE and antiphospholipid syndrome; and post-transfusion purpura.

Sequestration or Dilution

Hypersplenism, in which an enlarged spleen from portal hypertension, infiltration or infection pools platelets — usually a moderate drop, rarely below 50. Massive transfusion and large-volume fluid resuscitation cause dilutional thrombocytopaenia. Pregnancy causes a mild fall in around 8% of women (gestational thrombocytopaenia), which is benign and needs no action.

Pseudothrombocytopaenia must be excluded before anything else: EDTA in the sample tube causes platelets to clump in vitro, giving a spuriously low automated count in a person with entirely normal haemostasis. A blood film shows the clumps, and repeating the count in a citrate tube resolves it.

Mild thrombocytopaenia is usually asymptomatic and found incidentally on a blood count.

Bleeding from low platelets has a characteristic mucocutaneous pattern, distinct from the deep bleeding into joints and muscle seen in clotting factor deficiency: petechiae, which are pinpoint, non-blanching, and typically appear first on dependent areas and the lower legs; purpura and easy bruising; bleeding from gums and nose; menorrhagia; and prolonged bleeding from minor cuts.

More serious manifestations are gastrointestinal and urinary tract bleeding, and intracranial haemorrhage — rare but the principal cause of death, and the reason a severe headache in a profoundly thrombocytopaenic patient is an emergency.

Accompanying features point to the cause: fever and systemic upset suggest sepsis or acute leukaemia; splenomegaly suggests sequestration or a lymphoproliferative disorder; a pentad of fever, neurological signs, renal impairment, haemolytic anemia and thrombocytopaenia suggests TTP, which is a haematological emergency.

A blood film is mandatory and is the highest-yield investigation. It excludes pseudothrombocytopaenia, shows platelet size — large platelets suggesting active production and peripheral destruction — and reveals schistocytes in the microangiopathies, blasts in leukaemia, and dysplastic changes in myelodysplasia.

A full blood count establishes whether other lineages are affected: isolated thrombocytopaenia points to ITP, drugs, or hypersplenism, while pancytopenia points to marrow failure or infiltration. Coagulation studies distinguish DIC, in which PT and APTT are prolonged with low fibrinogen and raised D-dimer, from ITP, in which they are normal.

Further tests are guided by the picture: renal and liver function, LDH and haptoglobin for haemolysis, B12 and folate, HIV and hepatitis B and C serology, ANA, a pregnancy test, and ADAMTS13 activity where TTP is suspected. Helicobacter pylori testing is worthwhile in chronic ITP, since eradication improves the count in some patients. Bone marrow examination is reserved for suspected marrow disease, an atypical course, or older patients in whom myelodysplasia is a real possibility.

ITP remains a diagnosis of exclusion — there is no confirmatory test, and platelet antibody assays are not sufficiently reliable to establish it.

Chronic liver disease is a common and often overlooked contributor, acting through both hypersplenism and reduced thrombopoietin production. Autoimmune disease, particularly SLE and antiphospholipid syndrome, frequently coexists with ITP, as do thyroid disease and common variable immunodeficiency. Chronic ITP carries a treatment burden of its own: long-term corticosteroids bring osteoporosis, diabetes and cataract, and splenectomy brings lifelong risk of overwhelming encapsulated-organism sepsis, requiring vaccination and a clear plan for febrile illness.