Thrombocytopenia


Epidemiology

Incidence of Thrombocytopenia in the Intensive Care Unit (ICU) Setting

Clinical Studies

  • Systematic Review Reported that Thrombocytopenia Occurred in 8-68% of Patients at the Time of ICU Admission (Chest, 2011) [MEDLINE]
  • Systematic Review Reported that New-Onset Occurred During the ICU Stay in 13-44% of Patients (Chest, 2011) [MEDLINE]
    • Incidence of Thrombocytopenia was Correlated with the Severity of Illness, the Presence of Sepsis, and the Presence of Organ Dysfunction

Predictors of Developing Thrombocytopenia in the Intensive Care Unit (ICU) Setting (Crit Care Med, 2002) [MEDLINE] (Chest, 2013) [MEDLINE]

Most Common Etiologies of New-Onset Thrombocytopenia in the Intensive Care Unit (ICU) Setting (Crit Care Med, 2000) [MEDLINE]

  • General Comments
    • More Than One Etiology was Found in 26% of Cases
  • Sepsis (see Sepsis): 48% of cases
  • Sepsis with Documented Bacteremia (see Sepsis): 28% of cases
  • Liver Disease/Hypersplenism: 18% of cases
  • Overt Disseminated Intravascular Coagulation (DIC) (see Disseminated Intravascular Coagulation): 14% of cases
  • Unknown Etiology: 14% of cases
  • Infection: 11% of cases
  • Primary Hematologic Disorder: 9% of cases
  • Non-Cytotoxic Medications: 9% of cases
  • Cytotoxic Medications: 7% of cases
  • Massive Transfusion: 7% of cases
  • Other Etiologies: 7% of cases
  • Alcohol (Ethanol) Abuse (see Ethanol): 5% of cases


Etiology

Pseudothrombocytopenia

  • General Comments
    • In Vitro Artifact Due to Platelet Agglutination Via Antibodies (Usually, IgG, Also IgM and IgA) When the Calcium Content is Decreased by Blood Collection in Purple Top EDTA-Containing Blood Collection Tubes
    • If Suspected, Platelet Count Should Be Determined Using a Blue Top Sodium Citrate-Containing Tube, a Green Top Heparin-Containing Tube, or Via a Peripheral Smear of Fingerstick Blood
  • Antiphospholipid Antibody Syndrome (see Antiphospholipid Antibody Syndrome)
    • XXXX
  • Platelet Glycoprotein IIb IIIa Receptor Antagonists (see Platelet Glycoprotein IIb IIIa Receptor Antagonists)
    • Platelet Clumping Due to Ethylenediaminetetraacetic Acid (EDTA) in Collection Tube, Resulting Miscounting by Automated Detectors
    • Platelet Clumping Has Been Reported with All 3 Agents
    • EPIC Trial (J Am Coll Cardiol, 1997) [MEDLINE]
      • Incidence of Pseudothrombocytopenia with Abciximab was 1.1%, Whereas the Incidence of True Acute Thrombocytopenia was 2.7% with Abciximab (see Abciximab)
    • Collect Blood in Citrate Tubes
      • May Allow Accurate Counting in Some, But Not All, Cases of EDTA-Associated Clumping
    • Inspection of Smear
      • Gold Standard for Accurate Platelet Count
  • Multiple Myeloma (see Multiple Myeloma)
  • Platelet Cold Agglutinins

Impaired Platelet Production

  • Inherited Platelet Disorders
    • General Comments
      • Inherited platelet disorders can affect platelet number, platelet function, or both
        • These include syndromic disorders with other manifestations as well as disorders with isolated thrombocytopenia
      • Although these are lifelong disorders, they often are not diagnosed until adulthood, or they may be misdiagnosed as immune thrombocytopenia (ITP)
        • This was Illustrated in a Database Review from the McMaster Immune Thrombocytopenic Purpura Registry, Which Found That, of 295 Patients Initially Diagnosed with Primary Immune Thrombocytopenic Purpura, 5 Patients were Reclassified as Having an Inherited Platelet Disorder
    • Selected Inherited Platelet Disorders
      • Adenosine Diphosphate (ADP) Receptor Defect
      • Bernard-Soulier Syndrome
      • Chediak-Higashi Syndrome (see Chediak-Higashi Syndrome)
      • Congenital Amegakaryotic Hypoplasia (CAMT)
        • Rare Disorder Which Presents with Severe Thrombocytopenia and Absence of Megakaryocytes in the Bone Marrow
        • Some Patients are Homozygous for Mutations Which Produce an Inactive Thrombopoietin Receptor (c-Mpl) Leading to Minimal Platelet Production Similar to that Observed in c-Mpl Knockout Mice
        • Some Patients Ultimately Develop Bone Marrow Aplasia, Confirming the Multipotential Effect of Thrombopoietin Activity
      • Glanzmann Thrombasthenia (see xxxx)
      • Hermansky-Pudlak Syndrome (see xxxx)
      • Thrombocytopenia with Absent Radii (TAR) Syndrome
        • Selective Decrease in Platelet Production
  • Aplastic Anemia (see Aplastic Anemia)
    • Clinical
      • XXXXX
  • Bone Marrow Infiltration (Due to Leukemia/Lymphoma/Myeloproliferative/Lymphoproliferative Disorders)
    • Acute Lymphocytic Leukemia (ALL)(see Acute Lymphocytic Leukemia)
      • However, many patients with leukemia have both marrow infiltration and splenic sequestration
    • Acute Myeloid Leukemia (AML) (see Acute Myeloid Leukemia)
      • However, many patients with leukemia have both marrow infiltration and splenic sequestration
    • Chronic Lymphocytic Leukemia (CLL) (see Chronic Lymphocytic Leukemia)
      • However, many patients with leukemia have both marrow infiltration and splenic sequestration
    • Chronic Myeloid Leukemia (CML) (see Chronic Myeloid Leukemia)
      • However, many patients with leukemia have both marrow infiltration and splenic sequestration
    • Lymphoma (see Lymphoma)
      • However, many patients with lymphoma have both marrow infiltration and splenic sequestration
  • Deficiency
  • Hemophagocytic Lymphohistiocytosis (HLH) (see Hemophagocytic Lymphohistiocytosis)
    • XXXX
  • Infection
  • Myelodysplastic Syndrome (MDS) (see Myelodysplastic Syndrome)
  • Sepsis (see Sepsis)
    • Multiple Potential Mechanisms
      • Bone Marrow Suppression (Often Accompanied by Other Cytopenias)
      • Consumptive Coagulopathy Related to Sepsis-Induced Platelet Activation with/without Frank Disseminated Intravascular Coagulation (DIC) (see Disseminated Intravascular Coagulation)
      • Hemodilution Associated with Intravenous Fluid Resuscitation
      • Increased Circulating Histones (JAMA, 2016) [MEDLINE]
      • Increased Platelet Destruction
      • Platelet Sequestration
  • Drugs/Toxins-Chemotherapeutic Myelosuppressive Agents
  • Drugs/Toxins-Other
    • Estrogens (see Estrogen)
    • Ethanol (see Ethanol)
    • Ganciclovir (Cytovene) (see Ganciclovir)
    • Interferon Alfa
    • Linezolid (Zyvox) (see Linezolid)
      • Dose-Dependent Myelosuppression
    • Thiazide Diuretics (see Thiazides)
      • Chlorothiazide (see Chlorothiazide)
        • Suspected Etiology
      • Hydrochlorothiazide (HCTZ) (see Hydrochlorothiazide)
        • Suspected Etiology: usually mild (50-100k), but may persist for several months after discontinuation of drug
    • Tolbutamide (Orinase) (see Tolbutamide)
  • Other
    • Acquired Amegakaryocytic Thrombocytopenia
      • Rare Etiology in Which Autoantibodies to the Thrombopoietin Receptor on Megakaryocytes Can Result in Severe Thrombocytopenia
    • Liver Disease (see Cirrhosis)
      • Liver Produces Thrombopoietin, and Severe Liver Disease with Impaired Liver Synthetic Function (and Decreased Thrombopoietin Levels) Can Result in Thrombocytopenia
      • Note that Liver Disease Also Causes Compensatory Splenomegaly with Hypersplenism (Splenic Sequestration of Platelets) (See Below)
    • Paroxysmal Nocturnal Hemoglobinuria (PNH) (see Paroxysmal Nocturnal Hemoglobinuria)
      • XXXXXXXXXXXXX
    • Radiation Therapy (see Radiation Therapy)
      • XXXXXXXXXX

Splenic Platelet Sequestration/Hypersplenism (see Splenomegaly)

  • General Comments
    • Approximately one-third of the platelet mass is found in the spleen, in equilibrium with the circulating platelet pool (J Clin Invest, 1966) [MEDLINE])
    • With splenomegaly, a greater fraction of the total platelet mass is sequestered in the spleen (up to 90 percent of the total platelet mass), resulting in a decreased circulating platelet count
    • Thrombocytopenia from splenic pooling of platelets is typically mild to moderate (in the range of 60-100,000/μL)
      • Severe thrombocytopenia or bleeding in the setting of splenomegaly should prompt investigation for other causes
  • Liver Disease (see Cirrhosis)
    • Epidemiology
      • In a series of 354 patients with a presumptive diagnosis of nonalcoholic fatty liver disease, thrombocytopenia was seen in 29% (Clin Gastroenterol Hepatol, 2012) [MEDLINE]
    • Physiology
      • Portal Hypertension Results in Splenomegaly
      • In severe liver disease, platelets may also be decreased because of reduced thrombopoietin levels
  • Gaucher Disease (see Gaucher Disease)
    • Physiology
      • Splenic Infiltration with Macrophages Results in Splenomegaly
  • Splenic Infiltration with Tumor Cells
    • Physiology
      • Splenic Infiltration with Tumor Cells Results in Splenomegaly
    • Clinical
      • Acute Lymphocytic Leukemia (ALL) (see Acute Lymphocytic Leukemia_
        • However, Many Patients with Leukemia Have Both Marrow Infiltration and Splenic Sequestration
      • Acute Myeloid Leukemia (AML) (seeAcute Myeloid Leukemia)
        • However, Many Patients with Leukemia Have Both Marrow Infiltration and Splenic Sequestration
      • Chronic Lymphocytic Leukemia (see Chronic Lymphocytic Leukemia)
        • However, Many Patients with Leukemia Have Both Marrow Infiltration and Splenic Sequestration
      • Chronic Myeloid Leukemia (CML) (see Chronic Myeloid Leukemia)
        • However, Many Patients with Leukemia Have Both Marrow Infiltration and Splenic Sequestration
      • Lymphoma (see Lymphoma)
        • However, Many Patients with Lymphoma Have Both Marrow Infiltration and Splenic Sequestration

Dilutional Thrombocytopenia

  • Large-Volume Intravenous Fluid Resuscitation/Massive Transfusion
    • Massive fluid resuscitation or massive transfusion without proportionate transfusion of platelets can cause thrombocytopenia
    • In massive transfusion, platelet counts are reduced in proportion to the number of red blood cell (RBC) units transfused in a 24-hour period (Ann Surg, 1979) [MEDLINE] (Am J Clin Pathol, 1991) [MEDLINE]
    • If thrombocytopenia is mild, the patient can be observed until the platelet count recovers
    • If significant blood has been lost, platelet transfusions may be needed. Ratios of platelets to other products are discussed separately
    • Common Etiologies
      • Sepsis (see Sepsis)
        • Multiple Potential Mechanisms
        • Bone Marrow Suppression (Often Accompanied by Other Cytopenias)
        • Consumptive Coagulopathy Related to Sepsis-Induced Platelet Activation with/without Frank Disseminated Intravascular Coagulation (DIC) (see Disseminated Intravascular Coagulation)
        • Hemodilution Associated with Intravenous Fluid Resuscitation
        • Increased Circulating Histones (JAMA, 2016) [MEDLINE]
        • Increased Platelet Destruction
        • Platelet Sequestration
      • Trauma (see Trauma-General)
    • Physiology
      • Due to Dilution of Platelets
    • Clinical
  • Postoperative Thrombocytopenia
    • Postoperative Thrombocytopenia May Occur if There is Significant Consumption of Platelets During Surgery or in Wound Healing
    • Dilutional thrombocytopenia may also contribute
    • This is generally a diagnosis of exclusion made when other causes of thrombocytopenia are absent and the platelet count gradually Normalizes
  • Pregnancy (Gestational Thrombocytopenia) (see Pregnancy)
    • Physiology
      • Gestational Thrombocytopenia results from progressive expansion of the blood volume that typically occurs during pregnancy, leading to Hemodilution*
      • Cytopenias Result, Although Production of Blood Cells is Normal or Increased
    • Clinical
      • Platelet Counts <100k, However, are Observed in <10% of Pregnant Women in the Third Trimester
      • Decreases in Platelet Count to <70k Should Prompt Consideration of Pregnancy-Related ITP (See Above) as Well as Preeclampsia or a Pregnancy-Related Thrombotic Microangiopathy

Abnormal Platelet Distribution/Pooling

  • Hypothermia (see Hypothermia)
    • Physiology
      • Abnormal Platelet Distribution/Pooling
  • Sepsis (see Sepsis)
    • Multiple Potential Mechanisms
      • Bone Marrow Suppression (Often Accompanied by Other Cytopenias)
      • Consumptive Coagulopathy Related to Sepsis-Induced Platelet Activation with/without Frank Disseminated Intravascular Coagulation (DIC) (see Disseminated Intravascular Coagulation)
      • Hemodilution Associated with Intravenous Fluid Resuscitation
      • Increased Circulating Histones (JAMA, 2016) [MEDLINE]
      • Increased Platelet Destruction
      • Platelet Sequestration

Increased Platelet Destruction

Immune Thrombocytopenic Purpura (ITP) (see Immune Thrombocytopenic Purpura)

  • Primary/Idiopathic Thrombocytopenic Purpura
  • Secondary Immune Thrombocytopenic Purpura
    • Antiphospholipid Antibody Syndrome (see Antiphospholipid Antibody Syndrome)
    • Evan Syndrome (see Evan Syndrome)
    • Immunodeficiency
    • Infection
    • Inflammatory Bowel Disease (IBD)
    • Lymphoproliferative Disorder
    • Post-Transplant
    • Rheumatologic Disease
    • Drug/Vaccine/Toxin (see also https://www.ouhsc.edu/platelets/index.html)
      • α-Methyldopa (see α-Methyldopa)
      • β-Lactam/Cephalosporin Antibiotics (see β-Lactam Antibiotics)
      • 5-Fluorouracil (5-FU, Adrucil) (see 5-Fluorouracil)
      • Acetaminophen (Tylenol) (see Acetaminophen)
        • Antibodies React with an Acetaminophen Metabolite, Not the Unmodified Drug
      • Alemtuzumab (Campath, MabCampath, Campath-1H, Lemtrada) (see Alemtuzumab)
        • Thrombocytopenia Usually Presents Months After Drug Exposure and May Occur Even When the Patient is Not Actively on the Drug
        • May Respond to Standard Immune Thrombocytopenic Purpura (ITP) Therapies
      • Aminoglutethimide (Cytadren) (see Aminoglutethimide)
      • Aminosalicylic Acid
      • Amiodarone (Cordarone) (see Amiodarone)
      • Amphotericin B (see Amphotericin)
      • Antithymocyte Globulin (ATG) (see Antithymocyte Globulin)
      • Apronalide
      • Arsenical Drugs
        • Arsenical Drugs Have Historically Been Used to Treat Syphilis
        • Arsphenamine
        • Neoarsphenamine
        • Oxophenarsine Hydrochloride
      • Atezolizumab (Tecentriq) (see Atezolizumab)
      • Aztreonam (Azactam) (see Aztreonam)
      • Beans
      • Bisoprolol (Zebeta) (see Bisoprolol)
      • Captopril (Capoten) (see Captopril)
      • Carbamazepine (Tegretol) (see Carbamazepine)
      • Cetirizine (Zyrtec) (see Cetirizine)
      • Chlorpropamide (Diabinese) (see Chlorpropamide)
        • Suspected Etiology
      • Chloroquine (see Chloroquine)
        • Suspected Etiology
      • Cimetidine (Tagamet)(see Cimetidine)
      • Cinchona Alkaloids
        • Quinidine (see Quinidine)
        • Quinine (see Quinine)
        • Quinine Can Also Cause a Thrombotic Microangiopathy and/or Other Cytopenias
      • Danazol (Azol, Bonzol, Cyclomen, Danol, Nazol) (see Danazol)
      • Daptomycin (Cubicin) (see Daptomycin)
      • Dexamethasone (see Dexamethasone)
      • Diatrizoate Meglumine (Hypaque Meglumine)
      • Diazoxide
      • Digitoxin/Digoxin (see Digoxin)
      • Diltiazem (Cardizem) (see Diltiazem)
      • Dipyridamole (Persantine) (see Dipyridamole)
      • Durvalumab (Imfinzi) (see Durvalumab)
      • Ethambutol (see Ethambutol)
      • Ethosuximide (see Ethosuximide)
      • Exenatide (Byetta, Bydureon) (see Exenatide)
      • Famotidine (Pepcid) (see Famotidine)
      • Felbamate (Felbatol)
      • Filgrastim (Neupogen, Zarxio) (see Filgrastim)
      • Fluconazole (Diflucan, Trican) (see Fluconazole)
      • Furosemide (Lasix) (see Furosemide)
      • Gold (see Gold)
        • Thrombocytopenia May Persist After the Drug is Stopped
      • Glyburide (Diabeta, Micronase, Glynase) (see Glyburide)
      • Haloperidol (Haldol) (see Haloperidol)
      • Heparin-Induced Thrombocytopenia (HIT) (see Heparin-Induced Thrombocytopenia)
        • Heparin (Unfractionated) (see Heparin)
        • Dalteparin (Fragmin) (see Dalteparin)
        • Enoxaparin (Lovenox)* (see Enoxaparin)
        • Fondaparinux (Arixtra) (see Fondaparinux)
        • Although This is Actually a Factor Xa Inhibitor, There Have Been Case Reports of it Causing Heparin-Induced Thrombocytopenia (HIT)\
        • Nadroparin
        • Tinzaparin (Innohep) (see Tinzaparin)
      • Ipilimumab (Yervoy) (see Ipilimumab)
        • Thrombocytopenia May Occur Even When the Patient is Not Actively on the Drug
        • May Respond to Standard Immune Thrombocytopenic Purpura (ITP) Therapies
      • Irinotecan (Camptosar) (see Irinotecan)
      • Influenza Vaccine (see Influenza Virus)
      • Insecticides
        • Suspected Etiology
      • Intravenous Immunoglobulin (IVIG) (see Intravenous Immunoglobulin)
      • Iopanoic Acid
      • Leucovorin (see Leucovorin)
      • Levamisole (Ergamisol) (see Levamisole)
      • Measles-Mumps-Rubella (MMR) Vaccine
      • Methicillin (see Methicillin)
      • Mirtazapine (Remeron) (see Mirtazapine)
      • Natalizumab (Tysabri) (see Natalizumab)
      • Nivolumab (Opdivo) (see Nivolumab)
        • Thrombocytopenia May Occur Even When the Patient is Not Actively on the Drug
        • May Respond to Standard Immune Thrombocytopenic Purpura (ITP) Therapies
      • Nonsteroidal Anti-Inflammatory Agents (NSAID’s) (see Nonsteroidal Anti-Inflammatory Drug)
        • Aceclofenac
        • Aspirin (Acetylsalicylic Acid) (see Acetylsalicylic Acid)
        • Suspected Etiology
        • Diclofenac (Aclonac, Cataflam, Voltaren) (see Diclofenac)
        • Ibuprofen (see Ibuprofen)
        • In Some Patients, Antibodies React with the Unmodified Drug
        • In Some Patients, Antibodies Only React with a Drug Metabolite
        • Meclofenamic Acid (Meclomen) (see Meclofenamic Acid)
        • Naproxen (Naprosyn, Aleve) (see Naproxen)
        • Antibodies React with a Drug Metabolite, Not the Unmodified Drug
        • Oxyphenbutazone (Tandearil, Tanderil)
      • Novobiocin
      • Oseltamivir (Tamiflu) (see Oseltamivir)
      • Oxaliplatin (Eloxatin, Oxaliplatin Medac) (see Oxaliplatin)
      • P-Aminosalicylate
      • Pembrolizumab (Keytruda) (see Pembrolizumab)
        • Thrombocytopenia May Occur Even When the Patient is Not Actively on the Drug
        • May Respond to Standard Immune Thrombocytopenic Purpura (ITP) Therapies
      • Phenytoin (Dilantin) (see Phenytoin)
      • Platelet Glycoprotein IIb/IIIa Receptor Antagonists (see Platelet Glycoprotein IIb/IIIa Receptor Antagonists)
        • Abciximab (ReoPro) (see Abciximab)
        • Eptifibatide (Integrilin) (see Eptifibatide)
        • Tirofiban (Aggrastat) (see Tirofiban)
        • Epidemiology
        • In the EPIC Trial, the Incidence of Pseudothrombocytopenia with Abciximab was 1.1%, Whereas the Incidence of True Acute Thrombocytopenia was 2.7% with Abciximab
        • Physiology
        • Believed to Be Due to Preformed Antibodies Against Neoepitopes Exposed by Alteration of the GP IIb/IIIa Molecules
        • Clinical
        • Thrombocytopenia Can Occur in a Matter of Hours
      • Procainamide (Pronestyl) (see Procainamide)
      • Pyrazinamide (PZA) (see Pyrazinamide)
      • Quetiapine (Seroquel) (see Quetiapine)
      • Quinolone Antibiotics
      • Rifampin (Rifampicin, Rifadin) (see Rifampin)
      • Serotonin 5-HT3 Receptor Antagonists (see Serotonin 5-HT3 Receptor Antagonists)
      • Simvastatin (Zocor) (see Simvastatin)
      • Stibophen
      • Sulfonamides (see Sulfonamides)
        • Sulfadiazine: suspected etiology
        • Sulfisoxazole: suspected etiology
        • Sulfamerazine: suspected etiology
        • Sulfamethazine: suspected etiology
        • Sulfamethoxypyridazine: suspected etiology
        • Sulfamethoxazole (see Sulfamethoxazole-Trimethoprim)
        • Antibodies to Both Components of Trimethoprim/Sulfamethoxazole Have Been Identified
        • Sulfatolamide: suspected etiology
        • Sulfathiazole
      • Suramin
      • Tacrolimus (FK-506, Fujimycin, Prograf, Advagraf, Protopic, Hecoria, Astagraf XL) (see Tacrolimus)
      • Teicoplanin (see Teicoplanin)
      • Trastuzumab (see Herceptin)
      • Walnuts (see Walnuts)
      • Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT) (see Vaccine-Induced Immune Thrombotic Thrombocytopenia)
        • Rare Syndrome Which Occurs Approximately 5-30 Days Following Vaccination with a Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) Adenoviral Vector Vaccine (from AstraZeneca or Janssen)
        • May Manifest Life-Threatening Arterial and/or Venous Thromboses
      • Valproic Acid (see Valproic Acid)
      • Vancomycin (see Vancomycin)
        • In Addition to Parenteral Vancomycin, Vancomycin May Also Be Present in Orthopedic Cement Used in Joint Replacement
        • Vancomycin-Induced Anti-Platelet Antibodies (Either IgG or IgM) (NEJM, 2007) [MEDLINE]
      • Volanesorsen (Waylivra) (see Volanesorsen)
        • Unclear Mechanism

Non-Immune Platelet Destruction (Suspected Proapoptotic Effect) (Hematology Am Soc Hematol Educ Program, 2018) [MEDLINE]

Macroangiopathic Hemolytic Anemia (see Hemolytic Anemia)

Macroangiopathic Hemolytic Anemia (see Hemolytic Anemia)

Microangiopathic Hemolytic Anemia (MAHA) + Thrombocytopenia (see Hemoytic Thrombocytopenic Syndromes and Hemolytic Anemia)

Microangiopathic Hemolytic Anemia (MAHA) + Thrombocytopenia (see Hemoytic Thrombocytopenic Syndromes and Hemolytic Anemia)

  • General Comments
    • Immunologic Destructive Mechanism, Which Occurs Via Abnormal Vessels and/or Fibrin Thrombi
    • Microangiopathic Hemolytic Anemia (MAHA) is Caused by mechanical Red Blood Cell Fragmentation Which Occurs as Red Blood Cells Traverse Platelet-Rich Thrombi in the Microcirculation
      • The Result of Red Blood Cell Fragmentation is Schistocytes, Which Typically are Prominent on the Peripheral Blood Smear
    • Thrombocytopenia is Due to Platelet Consumption in Microthrombi Throughout the Microcirculation
      • Thrombocytopenia May Be Only Mild-Moderate in Many of the Primary Thrombotic Microangiopathy Syndromes, But in Patients with Thrombotic Thrombocytopenic Purpura (TTP), it is Typically Severe (Platelet Count is Almost Always <30,000/μL
  • Primary Thrombotic Microangiopathy Syndrome (see Thrombotic Microangiopathy)
  • Acute Pancreatitis (see Acute Pancreatitis)
    • Epidemiology
      • Case Reports (J Thromb Thrombolysis, 2020) [MEDLINE]
  • Adult-Onset Still’s Disease (see Adult-Onset Still’s Disease)
  • Disseminated Intravascular Coagulation (DIC) (see Disseminated Intravascular Coagulation)
  • Infection
  • Malignancy
    • Any Systemic Malignancy Can Cause Microangiopathic Hemolytic Anemia (MAHA) and Thrombocytopenia (Oncology-Williston Park, 2011) [MEDLINE]
      • In Some Patients, These Findings are Caused by Microvascular Metastases without Overt Evidence of Disseminated Intravascular Coagulation (DIC)
      • Most Commonly Associated Malignancies
  • Malignant Hypertension (see Hypertension)
    • Epidemiology
      • Severe Hypertension (Systolic Blood Pressure >220 mm Hg and/or Diastolic Blood Pressure >100 mm Hg) Can Cause Microangiopathic Hemolytic Anemia (MAHA) and Thrombocytopenia
    • Physiology
      • Abnormal Vessel Wall Resulting in Damage to Red Blood Cells
    • Diagnosis
      • Renal Biopsy (see Renal Biopsy)
        • Demonstrates Thrombotic Microangiopathy Identical to the Primary Thrombotic Microangiopathy Syndromes
    • Clinical
  • Rheumatologic Disease
    • Antiphospholipid Antibody Syndrome (see Antiphospholipid Antibody Syndrome)
      • Epidemiology
        • Especially Occurs with Catastrophic Antiphospholipid Antibody Syndrome (CAPS)
      • Clinical
        • Thrombocytopenia
    • Scleroderma (see Scleroderma)
      • Clinical
        • Mild Thrombocytopenia
    • Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus)
      • Physiology
        • Severe Vasculitis Resulting in Fibrin Deposition in Vessels with Damage to Platelets and Red Blood Cells
      • Clinical
        • Thrombocytopenia
  • Sepsis (see Sepsis)
    • Multiple Potential Mechanisms
      • Bone Marrow Suppression (Often Accompanied by Other Cytopenias)
      • Consumptive Coagulopathy Related to Sepsis-Induced Platelet Activation with/without Frank Disseminated Intravascular Coagulation (DIC) (see Disseminated Intravascular Coagulation)
      • Hemodilution Associated with Intravenous Fluid Resuscitation
      • Increased Circulating Histones (JAMA, 2016) [MEDLINE]
      • Increased Platelet Destruction
      • Platelet Sequestration
  • Severe Vitamin B12 Deficiency (see Vitamin B12)
    • Physiology
      • Vitamin B12 Deficiency Can Cause Ineffective Erythropoiesis and Thrombocytopenia, Which May Be Accompanied by Hemolysis and Red Blood Cell Morphology Resembling Microangiopathic Hemolytic Anemia (MAHA) (Pediatr Blood Cancer, 2009) [MEDLINE] (Am J Med, 2015) [MEDLINE] (CMAJ, 2023) [MEDLINE]
      • Retrospective Series of Patients with Vitamin B12 Deficiency (Br J Haematol, 2020) [MEDLINE]: n = 2,699
      • Approximately 0.6% of Cases Dad Findings Consistent with a Thrombotic Microangiopathy Including Schistocytes on the Peripheral Blood Smear, Thrombocytopenia, and/or Hemolysis with Increased Lactate Dehydrogenase (LDH)
      • Compared with a Matched Cohort of Patients with Thrombotic Thrombocytopenic Purpura, Those with Vitamin B12 Deficiency were More Likely to Have Teardrop Cells on the Peripheral Blood Smear, a Very High Lactate Dehydrogenase (LDH) Level, and a Lower PLASMIC Score
  • Transplant-Related Disease
    • Hematopoietic Stem Cell Transplant (HSCT) (Bone Marrow Transplant) (see Hematopoietic Stem Cell Transplant)
      • Epidemiology
        • May occur with autologous or allogeneic hematopoietic stem cell transplantation
        • May be associated with exposure to cytotoxic chemotherapy, radiation, systemic infection, or a calcineurin inhibitor
    • Renal Allograft Rejection (see Renal Allograft Rejection)
      • Epidemiology
        • Microangiopathic Hemolytic Anemia (MAHA) with Thrombocytopenia May Be Associated with Calcineurin Inhibitor Administration or Cytomegalovirus (CMV) Infection (Due to Immunosuppression)
      • Diagnosis
        • Renal Biopsy (see Renal Biopsy)
        • May Demonstrate Features of Rejection
      • Physiology
        • Abnormal Vessel Wall Resulting in Damage to Red Blood Cells
      • Clinical
        • Mild Thrombocytopenia
      • Prognosis
        • In Patients Who Have Received a Renal Transplant for a Primary Thrombotic Microangiopathy Syndrome, the Syndrome May Recur in the Transplanted Kidney

Other

Other

  • Postoperative Thrombocytopenia
    • Postoperative Thrombocytopenia May Occur if There is Significant Consumption of Platelets During Surgery or in Wound Healing
    • Dilutional Thrombocytopenia May Also Contribute
    • Postoperative Thrombocytopenia is Generally a Diagnosis of Exclusion Made When Other Etiologies of Thrombocytopenia are Absent and the Platelet Count Gradually Normalizes
  • Post-Transfusion Purpura (see Post-Transfusion Purpura)
    • Rare Disorder with Sudden-Onset Thrombocytopenia in Patient Who Recently Received Transfusion of Red Blood Cells, Platelets, or Plasma within 1 wk Prior to Detection of Thrombocytopenia
    • Antibodies Against the Human Platelet Antigen PlA1 are Detected in Most Patients
    • Patients with Post-Transfusion Purpura Almost Universally are Either Multiparous Women or Patients Who Have Received Transfusions Previously
    • Severe Thrombocytopenia and Bleeding is Typical
    • Initial Treatment Consists of Administration of IVIG (1 g/kg/d for 2 days)l, Which Should Be Administered as Soon as the Diagnosis is Suspected
    • Platelets are Not Indicated Unless Severe Bleeding is Present, But if They are Administered, HLA-Matched Platelets are Preferred
    • A Second Course or IVIG, Plasma Exchange, Corticosteroids, or Splenectomy May Be Used in Refractory Cases
    • PlA1-Negative or Washed Blood Products are Preferred for Subsequent Transfusions
  • Platelet Refractoriness (Due to Repeated Platelet Transfusions)
    • Repeat Transfusions Result in Antiplatelet Alloantibodies Resulting in Immune-Mediated Destruction of Future Transfused Platelets
  • Pregnancy (Gestational Thrombocytopenia) (see Pregnancy)
    • Physiology
      • Gestational Thrombocytopenia Results from Progressive Expansion of the Blood Volume that Typically Occurs During Pregnancy, Leading to Hemodilution
      • Cytopenias Result, Although Production of Blood Cells is Normal or Increased
    • Clinical
      • Platelet Counts <100k, However, are Observed in <10% of Pregnant Women in the Third Trimester
      • Decreases in Platelet Count to <70k Should Prompt Consideration of Pregnancy-Related ITP (See Above) as Well as Preeclampsia or a Pregnancy-Related Thrombotic Microangiopathy
  • Thrombosis
    • Large Thromboses Can Consume Platelets, Causing Transient Thrombocytopenia
    • This Typically occurs very early (within the first day or two) and is relatively mild, although more severe thrombocytopenia can occur
    • A series of four individuals with thrombocytopenia and an associated literature review documented platelet counts between 33,000 and 88,000/microL in the four with extensive venous thromboembolism (VTE) and platelet counts <150,000/microL in 10 percent of historical patients with a pulmonary embolus (mean platelet count, 293,000/microL (Am J Hematol, 2004) [MEDLINE]

Unknown/Other Mechanism

  • Bumetanide (Bumex)
    • Epidemiology
      • Rare Reports of Thrombocytopenia
  • Hepatic Sinusoidal Obstruction Syndrome (Hepatic Veno-Occlusive Disease) (see Hepatic Sinusoidal Obstruction Syndrome)
    • Epidemiology
      • XXXXX


Physiology

Normal Platelet Physiology

  • Normal Platelet Life Span: usually 7-10 days
  • Role of Spleen in Platelet Trafficking
    • Splenic Sequestration: approximately 33% of the total platelet mass is normally sequestered in the spleen
    • Splenectomy: will increase the platelet count by 33%
    • Splenomegaly: will increase the number of sequestered platelets


Diagnosis

Complete Blood Count (CBC) (see Complete Blood Count)

Thrombocytopenia

Peripheral Blood Smear (see Peripheral Blood Smear)

Bone Marrow Biopsy (see Bone Marrow Biopsy)


Clinical Locations of Hemorrhage


Clinical Patterns of Bleeding


Clinical Severity of Thrombocytopenia


Clinical Manifestations

Hemorrhagic Manifestations

Mucosal Hemorrhage

Ecchymosis (see Ecchymosis)

Petechiae (see Petechiae)

Purpura (see Purpura)

Procedural Hemorrhage

Pulmonary Manifestations

Increased Risk for Prolonged Invasive Mechanical Ventilation (see Invasive Mechanical Ventilation-Weaning)


Treatment

Management of Active Hemorrhage Associated with Thrombocytopenia

Address Factors Which May Contribute to Hemorrhage

Platelet Transfusion for Active Hemorrhage (see Platelet Transfusion)

Platelet Transfusion in Advance of an Invasive Procedures (see Platelet Transfusion)

Platelet Transfusion in Advance of an Invasive Procedures (see Platelet Transfusion)

Platelet Transfusion to Prevent Spontaneous Hemorrhage (see Platelet Transfusion)

General Comments

Recommendations for Thrombocytopenic Patients with Bone Marrow Suppression

Recommendations for Thrombocytopenic Patients with Immune Thrombocytopenic Purpura (ITP) (see xxxx)

Recommendations for Thrombocytopenic Patients with Thrombotic thrombocytopenic purpura (TTP) and heparin-induced thrombocytopenia (HIT)

Recommendations for Thrombocytopenic Patients with Liver Disease and Disseminated Intravascular Coagulation (DIC) (see Cirrhosis and Disseminated Intravascular Coagulation)

Clinical Efficacy


Prognosis

Thrombocytopenia and Mortality Rate in the Intensive Care Unit (ICU) Setting

  • Both a Low Nadir Platelet Count and a Large Fall in the Platelet Count Predict a Poor Outcome in Adult Intensive Care Unit Patients (Crit Care Med, 2000) [MEDLINE]
    • In a logistic regression analysis with ICU mortality as the dependent variable, the occurrence of thrombocytopenia had more explanatory power than admission variables, including APACHE II, SAPS II, and MODS scores (Adjusted Odds Ratio 4.2; 95% CI: 1.8-10.2)
  • In the Intensive Care Unit, Patients Who Develop Thrombocytopenia are More Likely to Bleed, Receive Transfusions, and Die (Chest, 2013) [MEDLINE]
    • Moderate and Severe Thrombocytopenia are Associated with Increased Intensive Care Unit and Hospital Mortality Rates


References

Epidemiology

Etiology

Physiology

Clinical

Treatment