Thrombocytopaenia

OVERVIEW

• definition of thrombocytopenia is a platelet count < 150 × 10E9/L
• most common haemostatic abnormality in ICU patients
• 15-60% incidence in ICU (higher in surgical/ trauma patients than medical)
• about 50% is pre-existing, otherwise it tends to occur in the first 4 days in ICU

PROGNOSIS

• increased mortality associated with severity of thrombocytopenia
• severity of thrombocytopenia correlates with prognostic scores (e.g. SAPS, MODS, APACHE)
• associated with increased hospital and ICU LOS

PATHOPHYSIOLOGY

• thrombopoietin produced by the liver and kidneys stimulates thrombopoiesis
• platelets are derived from megakaryocytes
• average platelet lifespan is 9 days, and destruction occurs by phagocytosis in the spleen and liver
• decreased production typically leads to a gradual fall in platelets over a week
• immune destruction typically leads to an abrupt fall in platelets
• aggregation is the main mechanism of thrombocytopenia in sepsis and MODS, sequestration also occurs in sepsis through binding to endothelium
• the spleen normally sequesters 1/3 of the body’s platelets, this increases to 90% in massive splenomegaly
• spleen contraction stimulated by the sympathetic nervous system can release additional platelets

CAUSES

Decreased production due to bone marrow failure (myelosuppression or infiltration)

• drugs (temporal association with starting a drug, typically improves a few days)
• alcohol
• infection (e.g. viruses such as rubella, mumps, varicella, CMV, EBV; chronic: HCV, HIV; tropical: Dengue, chikungunya)
• nutritional e.g. B12, folate, copper
• infiltration
• hematological disorders (e.g. leukemia)
• liver cirrhosis (decreased thrombopoietin)

Increased destruction

• sepsis
• immune – ITP e.g. post-viral, post-transfusion purpura, HITTS
• intravascular device (IABP, ECMO, PAC, bypass)
• drug induced (antibiotics, thiazides, H2 antagonists)
• antiphospholipid syndrome
• TTP
• HUS
• DIC
• HELLP
• haemolysis
• massive haemorrhage (consumption of platelets in clot formation)

Increased aggregation

• early sign of MODS
• sepsis (e.g. bacterial and fungal infections)
• massive PE
• thrombotic storm (widespread thrombosis in multiple organs)

Dilution

• post resuscitation
• massive transfusion (dilution in addition to consumption in haemorrhage)

Sequestration

• splenomegaly e.g. cirrhosis, congestive heart failure, portal hypertension, infection and myeloproliferative disorders

Spurious

• look for clumping on blood film

Often multifactorial in the critically ill (e.g. drug-induced thrombocytopenia amy not improve if sepsis then supervenes)

CLINICAL FEATURES

• often asymptomatic when first detected (significant or spontaneous bleeding rarely occurs with a platelet count > 50 × 10E9/L; 5-fold increase in risk <50 x 10E9/L)
• purpura, petechiae and bleeding
• bleeding from venepuncture sites
• Spontaneous intracerebral haemorrhage (<0.5% in ICU, higher risk if platelets <10 x 10E9/L)
• generalised edema (platelets are required for vascular integrity, thrombocytopenia contributes to capillary leak in the critically ill)

INVESTIGATIONS

Assess clinically for:

• drug history and timing of onset (e.g. abrupt drop in platelets within 2 weeks of transfusion or drugs)
• exposure to heparin (including line flushes and RRT)
• evidence of bleeding or microthrombosis
• splenomegaly

Investigations are tailored to the presentation and may include:

• blood film – clumping, schistocytes (microangiopathy), leukoerythroblastic profile (bone marrow disorder), RBC macrocytosis (B12, folate, EtOH, hypothyroidism)
• malaria screen (splenomegaly)
• Coagulation profile (DIC, sepsis, MODS)
• LFTs
• Haemolysis screen
• HIT screen
• vasculitis screen
• B12 and folate levels
• Septic screen
• Viral screen (e.g. HIV,HCV, EBV, CMV)
• investigation for source of bleeding if suspected

MANAGEMENT

• control bleeding
• treat underlying cause
• platelets best avoided in TTP and HITS unless active, life-threatening bleeding present
• As a rule of thumb, give 1 adult bag if:
  • platelets <10 x10E9/L
  • platelets <20 x10E9/L and patient has septic shock or is severely ill (expect ongoing consumption)
  • platelets <50 x10E9/L and an invasive interventional procedure is required
  • platelets <50 x10E9/L and patient requires anti-platelet drugs
  • platelets <100 x10E9 and severe traumatic brain injury / intracranial haemorrhage (Australian massive transfusion guidelines)
• platelets are also given for critical bleeding according to massive transfusion protocols

References and Links

Journal articles

• Crowther MA, Cook DJ, Meade MO, Griffith LE, Guyatt GH, Arnold DM, Rabbat CG, Geerts WH, Warkentin TE. Thrombocytopenia in medical-surgical critically ill patients: prevalence, incidence, and risk factors. J Crit Care. 2005 Dec;20(4):348-53. PMID: 16310606.
• Greinacher A, Selleng K. Thrombocytopenia in the intensive care unit patient. Hematology Am Soc Hematol Educ Program. 2010;2010:135-43. PMID: 21239783.
• Rice TW, Wheeler AP. Coagulopathy in critically ill patients: part 1: platelet disorders. Chest. 2009 Dec;136(6):1622-30. PMID: 19995764.
• Wang HL, Aguilera C, Knopf KB, Chen TM, Maslove DM, Kuschner WG. Thrombocytopenia in the intensive care unit. J Intensive Care Med. 2013 Sep-Oct;28(5):268-80. PMID: 22232201.