Thrombocytopaenia

James talks to Dr Shafqat Inam about thrombocytopaenia, or low platelet count, in this podcast.

Summary Writer:  Nicholas Malouf

Editor:  Shafqat Inam

Interviewee:  Shafqat Inam

About Dr Shafqat Inam

Shafqat Inam is currently a Haematology registrar at Royal Prince Alfred and Concord Hospitals, and Associate Lecturer at the University of Sydney. He studied medicine at the University of New South Wales and completed his junior medical officer and basic physician training at Royal Prince Alfred Hospital. Shafqat has a particular interest in research and medical education.

Thrombocytopaenia

With Dr Shafqat Inam, Haematology Registrar at Royal Prince Alfred and Concord Hospitals, New South Wales, Australia

Introduction

Thrombocytopaenia (low platelet count) is a common finding amongst inpatients and may occur due to a range of factors. It is often picked up incidentally as well as in the context of bleeding. A normal platelet count is 150 – 400 x 109/L. Degrees of thrombocytopaenia: mild 100 – 150 x 109/L; moderate 50 – 100 x 109/L; and severe< 50 x 109/L. The risk of severe spontaneous bleeding is greatly increased with platelets< 20 x 109/L. Evaluation of the patient with thrombocytopaenia ought to address both complications from low platelets and the aetiology of the condition.

Case 1

A patient was admitted overnight via the Emergency Department with fever on a background of prosthetic valve, IVDU and alcohol dependence. Their platelet count on admission was 40 (x109/L).

  • Consider the potential physiological causes of low platelet count
    • decreased bone marrow production
    • increased platelet destruction either by consumption or autoimmune process
    • sequestration such as in splenomegaly
  • Degree, trend and tempo
    • mild, moderate or severe
    • chase old blood tests
    • acute vs chronic
  • Key points in history
    • bone marrow disorders
    • autoimmune disorders
    • recent infections or at risk behaviour (HCV, HBV, HIV)
    • medications including antiplatelets, immunosuppressants and antibiotics
  • Examination
    • complications (bleeding, thrombosis in HITTS)
    • aetiology (signs of chronic liver disease, lymphadenopathy)
  • Idiosyncratic reactions
    • penicillins
    • vancomycin
  • Myelosuppressive agents
    • methotrexate
  • Immune-complex formation
    • heparin
    • LMWH
  • Antiplatelet agents (do NOT cause low platelet count but inhibit platelet function)
    • aspirin, clopidogrel (effects can last up to 7 days)
    • NSAIDs
  • Complications – classically mucocutaneous bleeding (cf. haemophilia)
    • oral mucosa & gums
    • petechiae& purpura
    • menorrhagia
    • gastro-intestinal bleeding
    • CNS bleeding (particularly in context of headstrike)
  • Aetiology
    • splenomegaly
    • lymphadenopathy
    • signs of chronic liver disease
  • For patients with an incidental finding of moderate isolated thrombocytopaenia tests beyond FBC are not usually required in hospital and can be ordered by a specialist in clinic.
    • This would include:
      • HBV, HCV and HIV serology
      • vitamin B12 and folate
      • autoimmune screen
      • serum EPG
      • bone marrow biopsy (only if significant concern of haematological malignancy)
    • Appropriate to monitor FBC every 2-3 days to observe trend of platelet count until recovering and/or cause has been determined
  • If thrombocytopaenia is detected in the context of bleeding or there are other blood count abnormalities further investigation in hospital is advised
  • Start to be concerned when PLT< 50
    • > 50, very low chance of spontaneous bleeding
    • for most surgical procedures >50 is sufficient (except neuroaxial or ocular procedures that usually require >100)
    • quite worried if PLT< 20 (especially <10)
  • Indications for transfusion of platelets
    • PLT< 50 with active bleeding
    • PLT< 20 and febrile
    • PLT < 10 with or without symptoms
    • part of massive transfusion protocol
    • immediately prior to surgical procedures to achieve goal PLT as described above
    • one pool of platelets increases PLT by 25 – 40
  • Situations when platelet transfusion is not safe
    • thrombotic thrombocytopaenic purpura (TTP)
    • heparin induced thrombotic thrombocytopaenia syndrome (HITTS)

Case 2

A 26-year-old female presents to the Emergency Department with petechiae on the shins, ankles and feet. Further history reveals recent easy bruising and menorrhagia. The platelet count is 12 x 109/L but WCC and Hb are normal.

  • Further history
    • recent viral infection
    • history of haematological issues
    • history of autoimmune conditions
    • recently commenced medications
    • previous blood counts
  • Further examination
    • oral mucosa looking for wet purpura
  • Most likely differential is idiopathic thrombocytopaenic purpura (ITP)
    • classically in young otherwise well women – may have an autoimmune phenotype (e.g. SLE, rheumatoid arthritis)
    • pathophysiology: autoimmune clearance of platelets
    • often triggered by recent viral illness
    • can follow a chronic course with gradual decline in platelet count
    • treated with immunosuppressants
  • Investigations
    • EUC and LFTs (largely as baseline before treatment but also screening for any other process)
    • Group &hold given risk of bleeding
    • there is no diagnostic test for ITP – diagnosis based on clinical presentation and exclusion of other causes
      • antiplatelet antibodies were done in the past but shown not to be useful
  • Treatment
    • Acute
      • corticosteroids – dexamethasone or prednisone (1mg/kg daily for 1-2 weeks then taper)
      • observe as inpatient for short period of time to ensure no severe bleeding
      • IVIg (if not responding to corticosteroids)
      • no use for platelet transfusion as platelets are rapidly consumed in ITP
  • Long-term
    • if platelet count remains low may add steroid sparing agents – azathioprine
    • may progress to splenectomy which can be curative for some patients

Case 3

A 72-year-old male is day 8 post elective coronary artery bypass grafting for coronary artery disease. He is on twice daily heparin for DVT prophylaxis. His platelet count has dropped to 80 from 190 pre-op. His left calf is swollen compared to the right.

  • Most likely differential is heparin induced thrombotic thrombocytopaenia syndrome (HITTS or HIT) however a full differential should be considered including infection and DIC (check D-Dimer and fibrinogen)
  • Pathophysiology of HITTS
    • autoantibody against heparin-platelet factor 4-complex
    • platelets therefore cleared by macrophages leading to thrombocytopaenia
    • paradoxically patients are at greater risk of thrombosis
      • mechanism not fully understood however HIT antibodies are thought to be able to activate platelets and hence trigger a clotting cascade
      • HITTS can also occur with LMWH (enoxaparin) although does so at a lower rate
  • Largely a clinical diagnosis then confirmed with antibody testing
  • Pre-test probability calculated with 4 T’s Score
    • degree of thrombocytopaenia
    • timing relative to heparin exposure
    • presence of thrombosis
    • other causes of thrombocytopaenia
      • each scored 0 to 2
      • if total score 0 to 3 – low probability
      • 4 or 5 – intermediate probability
      • 6 to 8 – high probability
  • Although not part of 4 T’s Score, patients may develop necrotic skin reaction at site of heparin injections
  • Immunological testing warranted if clinical suspicion is high enough (usually intermediate or high probability)
  • HITTS is a rare diagnosis and can be life-threatening – must be part of the differential of any patient on heparin with new thrombocytopaenia
  • Cease heparin if HITTS is suspected
  • Consult haematology for advice regarding alternative anticoagulation
  • Doppler ultrasound of lower limbs
    • thrombosis can be both venous and arterial
    • most commonly lower limb DVT or PE
    • arterial thrombosis can lead to gangrene
  • Thrombocytopaenia is common and carries a wide differential which can be narrowed with a focused history
  • Complications are usually related to bleeding however paradoxically in some conditions there is an increased risk of thrombosis (e.g. HITTS)
  • Important information when seeking haematology advice:
    • history or examination findings of active bleeding
    • history of viral infection, autoimmune conditions, haematological conditions and recent medications
    • previous FBC results

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Tags: #autoimmune disorders,#bleeding,#bone marrow disorders,#enoxaparin,#haematoglogy,#heparin,#HIT,#HITTS,#ITP,#LMWH,#low platelet count,#platelet,#purpura,#thrombocytopaenia,#thrombosis,#transfusion

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