Links To And Excerpts From The Internet Book Of Critical Care Chapter – Thrombocytopenia

In this post I link to and excerpt from The Internet Book of Critical Care [Link is to the complete table of contents] Chapter on Thrombocytopenia,  by 

Dr. Farkas gives us direct links to each part of his thrombocytopenia chapter:


Here are excerpts:

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overview & definition

  • Thrombocytopenia is extremely common in the ICU.  It is often a poor prognostic sign which is associated with systemic inflammation.
  • Most cases will resolve in parallel with the patient’s overall recovery.
when to initiate an evaluation?
  • Most ICU patients with mild thrombocytopenia don’t require an exhaustive evaluation.  Potential indications to evaluate further might include:
    • Severe thrombocytopenia (e.g. below ~50,000).
    • Features of HITT (abrupt drop in platelet count by >50%, skin necrosis at site of heparin injection).
    • Clinical thrombosis.
    • Underlying process is unclear, raising a possibility of an underlying hematologic disorder (e.g. thrombotic thrombocytopenic purpura or hemophagocytic lymphohistiocytosis).

common causes of thrombocytopenia in the ICU

Thrombocytopenia in critical illness may be divided into roughly four classes:

subacute/chronic thrombocytopenia:  often present before critical illness.

  • Cirrhosis, alcoholism
  • Bone marrow dysfunction (e.g. myelodysplastic syndrome)
  • Bone marrow suppression (chemotherapy, alcoholism, some antiviral agents, linezolid, some penicillins/cephalosporins, NSAIDs, thiazides)
  • HCV, HIV

non-immune consumption:  often gradual decrease over several days, adequate response to platelet transfusion.

  • Microangiopathic hemolytic anemia (TTP/HUS, HELLP, malignant hypertension)
  • Disseminated intravascular coagulation (DIC)
  • Catastrophic antiphospholipid antibody syndrome (CAPS)
  • Sepsis:  Can occur with any pathogen, but especially occurs with specific pathogens (ehrlichiosis, babesiosis, anaplasmosis, rocky mountain spotted fever, hantavirus, dengue)
  • Surgery, trauma
  • Hemophagocytic lymphohistiocytosis (HLH)
  • Devices:  intra-aortic balloon pump, hemodialysis, ECMO

immune consumption:  often occurs several days after ICU admission, decrease is rapid (>50% fall in 24-48 hours), often with severe thrombocytopenia which is poorly responsive to platelet transfusion.

  • HITT
  • Drug-induced immune thrombocytopenia (D-ITP; see section below)
  • Post-transfusional purpura
  • Passive alloimmune thrombocytopenia
  • Idiopathic thrombocytopenic purpura (ITP)1


  • Obvious causes
    • Massive transfusion
    • Hypothermia
  • Pseudo-thrombocytopenia
    • Artificially low platelet count due to in vitro aggregation induced by EDTA in blood tubes.
    • Diagnosed by finding clumped platelets on blood smear and higher platelet count when measured in a citrated blood tube (blue top platelet tube).
    • Usually meaningless, but can be associated with lupus, vasculitis, or lymphoma.2

clinical clues & specific situations*

*See the chapter for details

The differential diagnosis of thrombocytopenia is broad.  Below are some clues which may help point in the right direction.  These shouldn’t be used to narrow the differential diagnosis, but rather merely to highlight possibilities that deserve particular attention.

thrombocytopenia with (paradoxical) clinical thrombosis
severe thrombocytopenia (e.g., <20,000)5
thrombocytopenia in septic-appearing patient 
thrombocytopenia in the cardiac patient
thrombocytopenia in pregnant patient

drug-induced immune thrombocytopenia (D-ITP)

clinical features
  • Typically begins 1-3 weeks after starting new medication (can occur within a day if previously sensitized to medication).
  • Immune consumption often causes severe thrombocytopenia (e.g. <10,000-20,000) with bleeding.
  • Often causes systemic symptoms including fever and chills.4
commonly implicated medications
  • Cardiac:  Abciximab, Amiodarone, Amlodipine, Captopril, Digoxin, Diltiazem, Eptifibatide, Hydralazine, Procainamide, Quinidine, Simvastatin, Tirofiban,
  • Heme/onc:  Bleomycin, Fludarabine, Gemcitabine, Checkpoint inhibitors? (Ipilimumab), Oxaliplatin, Rituximab, Trastuzumab
  • Infectious disease:  Amphotercin B, Beta-lactams (esp. ampicillin, ceftriaxone, penicillin, piperacillin), Clarithromycin, Fluconazole, Fluoroquinolones (Ciprofloxacin, Levofloxacin, Moxifloxacin), Indinavir, Interferon-alpha, Linezolid, RifampinTrimethoprim/SulfamethoxazoleVancomycin
  • Nephrology:  Acetazolamide, Chlorothiazide, Desmopressin, Hydrochlorothiazide,
  • Neuro/Psych:  Carbamazepine, Clozapine, Diazepam, Fluoxetine, Haloperidol, Lamotrigine, Levetiracetam, Olanzapine, Ondansetron, Phenytoin, Quetiapine, Valproic acid
  • Rheum:  Allopurinol, Cyclosporin, Methotrexate, Tacrolimus, TNF-inhibitors (Adalimumab, Etanercept, Infliximab)
  • General/Misc:  Acetaimonphen, Aspirin, Danazol, H2 blockers (Famotidine, Ranitidine),  NSAIDs (esp. Diclofenac, Ibuprofen, Indomethacin, Naproxen), Pantoprazole, Quinine (found in tonic water, mixed drinks)
  • More information including more detailed up-to-date lists here.  Bolded drugs seem to be more common causes of D-ITP.
  • Discontinuation of drug.
  • May require platelet transfusion (however, ongoing consumption can be refractory to platelet transfusion).
  • IVIG may be used in severe cases (e.g. 1 gram/kg on two consecutive days).

transfusion related thrombocytopenias

heparin induced thrombocytopenia and thrombosis (HITT)*

*See the Chapter for details.

investigation of thrombocytopenia

chart review
  • Chronicity of thrombocytopenia?   (Obtaining baseline CBC from prior admissions or from other hospitals may be extremely helpful.)
  • Medication review?  (Many drugs can cause thrombocytopenia, not all of which are listed above.)
  • Calculate the 4T score for HITT (see above)
  • Recent events known to cause thrombocytopenia (e.g. massive transfusion, surgery, hemodialysis, intra-aortic balloon pump, ECMO, transfusion)?
thrombocytopenia tests to consider:  
  • Core investigations
    • Platelet count in citrated tube to exclude pseudothrombocytopenia (blue top tube)
    • Blood smear
    • Coagulation studies (INR, PTT)
    • DIC labs (fibrinogen, D-dimer)
  • Additional studies to consider
    • Heparin-PF4 antibody to evaluate for HITT if the 4T score is 4-8
    • Ferritin, if concern for hemophagocytic lymphohistiocytosis (HLH)
    • Ultrasonography to evaluate for DVT (if HITT or other thrombogenic forms of thrombocytopenia are possible)
    • Liver function tests, if concern for cirrhosis
    • Thromboelastography (TEG) may be considered in selected cases.14
immediate management steps to consider (while awaiting labs)
  • Discontinue heparin if there is concern for HITT.
  • Discontinue other potentially causative drugs if possible.
  • Review all anti-coagulating medications and consider holding them, if there is concern for possible hemorrhage (especially anti-platelet drugs).
  • Consider platelet transfusion (next section).

platelet transfusion

indications & contraindications to platelet transfusion 
  • Relative contraindications to platelet transfusion:
    • HITT
    • TTP/HUS
    • DIC with clinical thrombosis
  • Conventional transfusion targets:
    • Target >100 if active intracranial hemorrhage or pre-operative before neurosurgery/ophthalmic surgery.
    • Target >50 if active bleeding or pre-operative (non-neurologic surgery).
    • Target >20 possibly in patients with other coagulopathies (e.g. DIC, severe renal dysfunction).5
    • Target >10 in most patients.
response to platelet transfusion
  • Platelets may be given in one of the forms listed below, which are functionally equivalent.  Either one should increase platelet count by roughly 30,000-60,000.
    • 4-6 pack of pooled platelets from multiple donors.
    • One unit of platelets obtained using apheresis from a single person.
  • If the patient doesn’t respond appropriately to platelet transfusion, this may be investigated by checking a platelet level one hour after the next platelet transfusion.
    • If the 1-hour platelet level fails to increase appropriately, this implies immune platelet consumption.   In addition to the causes of immune platelet consumption listed above, this can also be due to alloimmunization (antibodies against donor platelet antigens).  Alloimmunization may be managed by obtaining HLA-matched platelets (with the help of the blood bank).
    • If the 1-hour platelet level increases appropriately and then platelet count falls over the following day, this indicates non-immune platelet consumption (causes listed above).


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