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
• Anti-Phospholipid Antibody Syndrome (see Anti-Phospholipid Antibody Syndrome, [[Anti-Phospholipid Antibody Syndrome]])
• IIb/IIIa Inhibitors (see IIb IIIa Inhibitors, [[IIb IIIa Inhibitors]]): platelet clumping due to EDTA in collection tube -> miscounting on automated detectors
  • Agents: platelet clumping has been reported with all 3 agents
    • Abciximab (ReoPro) (see Abciximab, [[Abciximab]])
    • Eptifibatide (Integrilin) (see Eptifibatide, [[Eptifibatide]])
    • Tirofiban (Aggrastat) (see Tirofiban, [[Tirofiban]])
  • EPIC Trial: incidence of pseudothrombocytopenia with abciximab was 1.1%, whereas the incidence of true acute thrombocytopenia was 2.7% with 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, [[Multiple Myeloma]])
• Platelet Cold Agglutinins

Impaired Platelet Production

• Aplastic Anemia (see Aplastic Anemia, [[Aplastic Anemia]])
• Bone Marrow Infiltration (due to Leukemia/Lymphoma/Myeloproliferative/Lymphoproliferative Disorders)
  • Acute Lymphocytic Leukemia (ALL)(see Acute Lymphocytic Leukemia, [[Acute Lymphocytic Leukemia]])
    • However, many patients with leukemia have both marrow infiltration and splenic sequestration
  • Acute Myeloid Leukemia (AML) (see Acute Myeloid Leukemia, [[Acute Myeloid Leukemia]])
    • However, many patients with leukemia have both marrow infiltration and splenic sequestration
  • Chronic Lymphocytic Leukemia (CLL) (see Chronic Lymphocytic Leukemia, [[Chronic Lymphocytic Leukemia]])
    • However, many patients with leukemia have both marrow infiltration and splenic sequestration
  • Chronic Myeloid Leukemia (CML) (see Chronic Myeloid Leukemia, [[Chronic Myeloid Leukemia]])
    • However, many patients with leukemia have both marrow infiltration and splenic sequestration
  • Lymphoma (see Lymphoma, [[Lymphoma]])
    • However, many patients with lymphoma have both marrow infiltration and splenic sequestration
• Deficiency
  • Folate Deficiency (see Folate, [[Folate]])
  • Vitamin B12 Deficiency (see Vitamin B12, [[Vitamin B12]])
• Chemotherapeutic Myelosuppressive Drugs: commonly cause impaired megakaryocyte proliferation and maturation
  • Severe Myelosuppression
    • Cytarabine (ARA-C, Cytosar-U) (see Cytarabine, [[Cytarabine]])
    • Daunorubicin (Daunomycin, Cerubidine) (see Daunorubicin, [[Daunorubicin]])
  • Moderate Myelosuppression
    • Busulfan (see Busulfan, [[Busulfan]])
    • Cyclophosphamide (Cytoxan) (see Cyclophosphamide, [[Cyclophosphamide]])
    • Mercaptopurine (6-Mercaptopurine) (see Mercaptopurine, [[Mercaptopurine]])
    • Methotrexate (see Methotrexate, [[Methotrexate]])
  • Mild Myelosuppression
    • Vinca Alkaloids
      • Vinblastine (see Vinblastine, [[Vinblastine]])
      • Vincristine (see Vincristine, [[Vincristine]])
      • Vinorelbine (see Vinorelbine, [[Vinorelbine]])
• Others Drugs/Toxins
  • Estrogens (see Estrogen, [[Estrogen]])
  • Ethanol (see Ethanol, [[Ethanol]])
  • Thiazide Diuretics (see Hydrochlorothiazide, [[Hydrochlorothiazide]])
• Infection
  • Cytomegalovirus (CMV) (see Cytomegalovirus, [[Cytomegalovirus]])
  • Human Immunodeficiency Virus (HIV) (see Human Immunodeficiency Virus, [[Human Immunodeficiency Virus]])
  • Parvovirus B19 (see Parvovirus B19, [[Parvovirus B19]])
• Myelodysplastic Syndromes (see Myelodysplastic Syndrome, [[Myelodysplastic Syndrome]])
• Other
  • Acquired Pure Megakaryocytic Thrombocytopenia
  • Congenital Amegakaryotic Hypoplasia: selective decrease in platelet production
  • Paroxysmal Nocturnal Hemoglobinuria (PNH) (see Paroxysmal Nocturnal Hemoglobinuria, [[Paroxysmal Nocturnal Hemoglobinuria]])
  • Radiation Therapy (see xxxx, [[xxxx]])
  • Thrombocytopenia with Absent Radii (TAR) Syndrome: selective decrease in platelet production

Splenic Platelet Sequestration/Hypersplenism (see Splenomegaly, [[Splenomegaly]])

• Cirrhosis/End-Stage Liver Disease (see End-Stage Liver Disease, [[End-Stage Liver Disease]])
  • Physiology: portal hypertension results in splenomegaly
• Gaucher’s Disease (see Gaucher’s Disease, [[Gauchers Disease]])
  • Physiology: splenic infiltration with macrophages -> splenomegaly
• Leukemia/Lymphoma/Myeloproliferative/Lymphoproliferative Disorders: splenic infiltration with tumor cells -> splenomegaly
  • Acute Lymphocytic Leukemia (ALL) (see Acute Lymphocytic Leukemia, [[Acute Lymphocytic Leukemia]]): however, many patients with leukemia have both marrow infiltration and splenic sequestration
  • Acute Myeloid Leukemia (AML) (seeAcute Myeloid Leukemia, [[Acute Myeloid Leukemia]]): however, many patients with leukemia have both marrow infiltration and splenic sequestration
  • Chronic Lymphocytic Leukemia (see Chronic Lymphocytic Leukemia, [[Chronic Lymphocytic Leukemia]]): however, many patients with leukemia have both marrow infiltration and splenic sequestration
  • Chronic Myeloid Leukemia (CML) (see Chronic Myeloid Leukemia, [[Chronic Myeloid Leukemia]]): however, many patients with leukemia have both marrow infiltration and splenic sequestration
  • Lymphoma (see Lymphoma, [[Lymphoma]]): however, many patients with lymphoma have both marrow infiltration and splenic sequestration

Abnormal Platelet Distribution/Pooling

• Hypothermia (see Hypothermia, [[Hypothermia]])
• Massive Transfusion
  • Epidemiology: particularly in the trauma setting (see Trauma-General, [[Trauma-General]])
  • Physiology: due to dilution of platelets
    • Transfusion of Fresh Frozen Plasma (FFP) (see Fresh Frozen Plasma, [[Fresh Frozen Plasma]])
    • Transfusion of Packed Red Blood Cells (see Packed Red Blood Cells, [[Packed Red Blood Cells]])

Increased Platelet Destruction

Drug/Toxin (see also http://www.ouhsc.edu/platelets/index.html)

• Acetaminophen (Tylenol) (see Acetaminophen, [[Acetaminophen]])
• Aminoglutethimide (Cytadren) (see Aminoglutethimide, [[Aminoglutethimide]])
• Aminosalicylic Acid
• Amiodarone (Cordarone) (see Amiodarone, [[Amiodarone]])
• Amphotericin B (see Amphotericin, [[Amphotericin]])
• Ampicillin (see Ampicillin, [[Ampicillin]])
• Apronalide
• Arsenical Drugs: used to treat syphilis
• Aspirin (Acetylsalicylic Acid) (see Acetylsalicylic Acid, [[Acetylsalicylic Acid]]): suspected etiology
• Beans
• Captopril (Capoten)) (see Captopril, [[Captopril]])
• Carbamazepine (Tegretol) (see Carbamazepine, [[Carbamazepine]])
• Chlorpropamide (Diabinese) (see Chlorpropamide, [[Chlorpropamide]]): suspected etiology
• Chloroquine (see Chloroquine, [[Chloroquine]]): suspected etiology
• Chlorothiazide (see Chlorothiazide, [[Chlorothiazide]]): suspected etiology
• Cimetidine (Tagamet)(see Cimetidine, [[Cimetidine]])
• Danazol ((Azol, Bonzol, Cyclomen, Danol, Nazol) (see Danazol, [[Danazol]])
• Diatrizoate Meglumine (Hypaque Meglumine)
• Diclofenac (Aclonac, Cataflam, Voltaren) (see Diclofenac, [[Diclofenac]])
• Digitoxin/Digoxin (see Digoxin, [[Digoxin]])
• Dipyridamole (Persantine) (see Dipyridamole, [[Dipyridamole]])
• Ethambutol (see Ethambutol, [[Ethambutol]])
• Famotidine (Pepcid) (see Famotidine, [[Famotidine]])
• Fluconazole (Diflucan, Trican) (see Fluconazole, [[Fluconazole]])
• Furosemide (Lasix) (see Furosemide, [[Furosemide]])
• Gold (see Gold, [[Gold]]): suspected etiology
• Glyburide (Diabeta, Micronase, Glynase) (see Glyburide, [[Glyburide]])
• Heparin-Induced Thrombocytopenia (HIT) (see Heparin-Induced Thrombocytopenia, [[Heparin-Induced Thrombocytopenia]])
  • Heparin (Unfractionated) (see Heparin, [[Heparin]])
  • Dalteparin (Fragmin) (see Dalteparin, [[Dalteparin]])
  • Enoxaparin (Lovenox) (see Enoxaparin, [[Enoxaparin]])
  • Fondaparinux (Arixtra) (see Fondaparinux, [[Fondaparinux]]): although this is actually a factor Xa inhibitor, there have been case reports of it causing HIT
  • Tinzaparin (Innohep) (see Tinzaparin, [[Tinzaparin]])
• Hydrochlorothiazide (HCTZ) (see Hydrochlorothiazide, [[Hydrochlorothiazide]]): suspected etiology -> usually mild (50-100k), but may persist for several months after discontinuation of drug
• Ibuprofen (see Ibuprofen, [[Ibuprofen]])
• IIb/IIIa Inhibitors (see IIb IIIa Inhibitors, [[IIb IIIa Inhibitors]]): abciximab, eptifibatide, 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: can occur in a matter of hours
• Imipenem (see Imipenem, [[Imipenem]])
• Insecticides: suspected etiology
• Iopanoic Acid
• Levamisole (Ergamisol) (see Levamisole, [[Levamisole]])
• Linezolid (Zyvox) (see Linezolid, [[Linezolid]])
• Meclofenamate
• Methicillin
• Methyldopa (see Methyldopa, [[Methyldopa]])
• Nalidixic Acid (see Nalidixic Acid, [[Nalidixic Acid]])
• Naproxen (Naprosyn, Aleve) (see Naproxen, [[Naproxen]])
• Novobiocin
• Oxyphenbutazone
• P-Aminosalicylate
• Phenytoin (Dilantin) (see Phenytoin, [[Phenytoin]])
• Piperacillin (see Piperacillin-Tazobactam, [[Piperacillin-Tazobactam]])
• Procainamide (Pronestyl) (see Procainamide, [[Procainamide]])
• Quinidine (see Quinidine, [[Quinidine]]): cinchona alkaloid
• Quinine (see Quinine, [[Quinine]]): cinchona alkaloid
• Rifampin (see Rifampin, [[Rifampin]])
• Simvastatin (Zocor) (see Simvastatin, [[Simvastatin]])
• Stibophen
• Sulfonamides (see Sulfonamides, [[Sulfonamides]])
  • Sulfadiazine: suspected etiology
  • Sulfisoxazole: suspected etiology
  • Sulfamerazine: suspected etiology
  • Sulfamethazine: suspected etiology
  • Sulfamethoxypyridazine: suspected etiology
  • Sulfamethoxazole (see Sulfamethoxazole-Trimethoprim, [[Sulfamethoxazole-Trimethoprim]]): suspected etiology
  • Sulfatolamide: suspected etiology
  • Sulfathiazole
• Tamoxifen (see Tamoxifen, [[Tamoxifen]])
• Valproic Acid (see Valproic Acid, [[Valproic Acid]])
• Vancomycin (see Vancomycin, [[Vancomycin]])

Immune Thrombocytopenic Purpura (ITP) (see Immune Thrombocytopenic Purpura, [[Immune Thrombocytopenic Purpura]])

• Primary/Idiopathic Thrombocytopenic Purpura
• Secondary Immune Thrombocytopenic Purpura
  • Autoimmune Disease
    • Anti-Phospholipid Antibody Syndrome (see Anti-Phospholipid Antibody Syndrome, [[Anti-Phospholipid Antibody Syndrome]])
    • Systemic Lupus Erythematosus (see Systemic Lupus Erythematosus, [[Systemic Lupus Erythematosus]])
  • Common Variable Immunodeficiency (CVID) (see Common Variable Immunodeficiency, [[Common Variable Immunodeficiency]])
  • Evan’s Syndrome (see Evans Syndrome, [[Evans Syndrome]])
  • Infection: infections can impair both platelet production and platelet survival
    • Cytomegalovirus (CMV) (see Cytomegalovirus, [[Cytomegalovirus]])
    • Helicobacter Pylori (see Helicobacter Pylori, [[Helicobacter Pylori]])
    • Hepatitis C (HCV) (see Hepatitis C Virus, [[Hepatitis C Virus]])
    • Human Immunodeficiency Virus (HIV) (see Human Immunodeficiency Virus, [[Human Immunodeficiency Virus]])
    • Infectious Mononucleosis (see Epstein-Barr Virus, [[Epstein-Barr Virus]])
    • Varicella-Zoster Virus (VZV) (see Varicella-Zoster Virus, [[Varicella-Zoster Virus]])
    • Other Infections
  • Lymphoproliferative Disorder
    • Autoimmune Lymphoproliferative Syndrome (Canale-Smith Syndrome) (see Autoimmune Lymphoproliferative Syndrome, [[Autoimmune Lymphoproliferative Syndrome]])
    • Chronic Lymphocytic Leukemia (CLL) (see Chronic Lymphocytic Leukemia, [[Chronic Lymphocytic Leukemia]])
    • Hodgkin’s Disease (see Hodgkins Disease, [[Hodgkins Disease]])
    • Lymphoma (see Lymphoma, [[Lymphoma]])
  • Post-Transplant
    • Bone Marrow Transplant (see Bone Marrow Transplant, [[Bone Marrow Transplant]])
    • Solid Organ Transplant
  • Post-Vaccination
    • Measles-Mumps-Rubella (MMR) Vaccine

Macroangiopathic Hemolytic Anemia

• Cardiac Hemolysis
  • Aortic Aneurysm (see Thoracic Aortic Aneurysm, [[Thoracic Aortic Aneurysm]] and Abdominal Aortic Aneurysm, [[Abdominal Aortic Aneurysm]]))
    • Physiology: xxx
  • Cardiopulmonary Bypass (CPB) (see Cardiopulmonary Bypass, [[Cardiopulmonary Bypass]])
    • Physiology: xxxx
  • Extracorporeal Membrane Oxygenation (ECMO) (see Extracorporeal Membrane Oxygenation, [[Extracorporeal Membrane Oxygenation]])
    • Physiology: fibrin stranding in oxygenator -> platelet consumption

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

• General Comments: on-immunologic destructive mechanism, which occurs via abnormal vessels and/or fibrin thrombi
• Primary Thrombotic Microangiopathy Syndrome (see Thrombotic Microangiopathy, [[Thrombotic Microangiopathy]])
  • Hereditary Thrombotic Microangiopathy
    • Hereditary Thrombotic Thrombocytopenic Purpura (Hereditary TTP) (Upshaw–Schulman Syndrome) (see Thrombotic Thrombocytopenic Purpura-Hereditary, [[Thrombotic Thrombocytopenic Purpura-Hereditary]])
    • Complement-Mediated Hemolytic-Uremic Syndrome (see Complement-Mediated Hemolytic-Uremic Syndrome, [[Complement-Mediated Hemolytic-Uremic Syndrome]])
    • Metabolism-Mediated Hemolytic-Uremic Syndrome
    • Coagulation-Mediated Hemolytic-Uremic Syndrome
  • Acquired Thrombotic Microangiopathy
    • Acquired Thrombotic Thrombocytopenic Purpura (Hereditary TTP) (see Thrombotic Thrombocytopenic Purpura-Acquired, [[Thrombotic Thrombocytopenic Purpura-Acquired]])
    • Shiga Toxin-Producing Escherichia Coli Hemolytic-Uremic Syndrome (see Shiga Toxin-Producing Escherichia Coli Hemolytic-Uremic Syndrome, [[Shiga Toxin-Producing Escherichia Coli Hemolytic-Uremic Syndrome]])
    • Drug-Induced Thrombotic Microangiopathy (see Drug-Induced Thrombotic Microangiopathy, [[Drug-Induced Thrombotic Microangiopathy]])
    • Complement-Mediated Hemolytic-Uremic Syndrome (see Complement-Mediated Hemolytic-Uremic Syndrome, [[Complement-Mediated Hemolytic-Uremic Syndrome]])
• Adult-Onset Still’s Disease (see Adult-Onset Still’s Disease, [[Adult-Onset Stills Disease]])
• Disseminated Intravascular Coagulation (DIC) (see Disseminated Intravascular Coagulation, [[Disseminated Intravascular Coagulation]])
  • Clinical
    • Thrombocytopenia (see Thrombocytopenia, [[Thrombocytopenia]])
    • Hemolysis: variable
    • Less severe than TTP usually
• Giant Hemangioma (Kasabach-Merritt Syndrome) (see Kasabach-Merritt Syndrome, [[Kasabach-Merritt Syndrome]])
  • Physiology: abnormal vessel wall -> damage to RBC
  • Clinical: mild thrombocytopenia
• Infection: these are characterized by MAHA with thrombocytopenia
  • Aspergillus (see Aspergillus, [[Aspergillus]])
  • Babesiosis (see Babesiosis, [[Babesiosis]])
  • Blastomycosis (see Blastomycosis, [[Blastomycosis]])
  • Borrelia (see Borrelia, [[Borrelia]])
  • Brucellosis (see Brucellosis, [[Brucellosis]])
  • Candida Albicans (see Candida, [[Candida]])
  • Chlamydia (see Chlamydia, [[Chlamydia]])
  • Clostridium Difficile (see Clostridium Difficile, [[Clostridium Difficile]])
  • Coxsackie Virus (see Coxsackie Virus, [[Coxsackie Virus]])
  • Cryptococcosis (see Cryptococcosis, [[Cryptococcosis]])
  • Cytomegalovirus (CMV) (see Cytomegalovirus, [[Cytomegalovirus]])
  • Dengue Virus (see Dengue Virus, [[Dengue Virus]])
  • Endocarditis (see Endocarditis, [[Endocarditis]])
  • Ehrlichiosis (see Ehrlichiosis, [[Ehrlichiosis]])
  • Epstein-Barr Virus (EBV) (see Epstein-Barr Virus, [[Epstein-Barr Virus]])
  • Hepatitis Viruses
  • Human Herpesvirus 6 (see Human Herpesvirus 6, [[Human Herpesvirus 6]])
  • Human Immunodeficiency Virus (HIV) (see Human Immunodeficiency Virus, [[Human Immunodeficiency Virus]])
  • Influenza A (see Influenza Virus, [[Influenza Virus]])
  • Legionellosis (see Legionellosis, [[Legionellosis]])
  • Leptospirosis (see Leptospirosis, [[Leptospirosis]])
  • Malaria (see Malaria, [[Malaria]])
  • Mycobacteria (see Mycobacteria, [[Mycobacteria]])
  • Norovirus (see Norovirus, [[Norovirus]])
  • Parvovirus B19 (see Parvovirus B19, [[Parvovirus B19]])
  • Rocky Mountain Spotted Fever (see Rocky Mountain Spotted Fever, [[Rocky Mountain Spotted Fever]])
  • Varicella-Zoster Virus (VZV) (see Varicella-Zoster Virus, [[Varicella-Zoster Virus]])
• Malignant Hypertension (see Hypertension, [[Hypertension]])
  • Physiology: abnormal vessel wall -> damage to RBC
  • Clinical
    • Acute Kidney Injury (AKI) (see Acute Kidney Injury, [[Acute Kidney Injury]]): variable
    • Mild Thrombocytopenia (see Thrombocytopenia, [[Thrombocytopenia]])
• Metastatic Carcinoma: due to activation of multifocal clotting -> hemolysis and thrombocytopenia
  • Multiple Pulmonary Metastases from Adenocarcinoma
  • Multiple Pulmonary Metastases from Lymphoma
• Pregnancy-Related Disorders
  • HELLP (Hemolysis, Elevated Liver Enzymes, and Low Platelets) Syndrome (see HELLP Syndrome, [[HELLP Syndrome]])
  • Pre-Eclampsia/Eclampsia (see Pre-Eclampsia, Eclampsia, [[Pre-Eclampsia, Eclampsia]])
• Rheumatologic Disease
  • Anti-Phospholipid Antibody Syndrome (see Anti-Phospholipid Antibody Syndrome, [[Anti-Phospholipid Antibody Syndrome]])
    • Clinical: thrombocytopenia
  • Scleroderma (see Scleroderma, [[Scleroderma]])
    • Clinical: mild thrombocytopenia
  • Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus, [[Systemic Lupus Erythematosus]])
    • Physiology: severe vasculitis -> fibrin deposition in vessels with damage to platelets and RBC
    • Clinical: thrombocytopenia (see Thrombocytopenia, [[Thrombocytopenia]])
• Severe Vitamin B12 Deficiency (see Vitamin B12, [[Vitamin B12]])
• Transplant-Related Disease
  • Bone Marrow Transplant/Stem Cell Transplant (see Bone Marrow Transplant, [[Bone Marrow Transplant]])
  • Renal Allograft Rejection (see Renal Allograft Rejection, [[Renal Allograft Rejection]])
    • Physiology: abnormal vessel wall -> damage to RBC
    • Clinical: mild thrombocytopenia (see Thrombocytopenia, [[Thrombocytopenia]])
• Vasculitis (see Vasculitis, [[Vasculitis]])

Other

• Post-Transfusion Purpura (see Post-Transfusion Purpura, [[Post-Transfusion Purpura]]): rare disorder with sudden-onset thrombocytopenia in patient who recently received transfusion of red cells, platelets, or plasma within 1 week prior to detection of thrombocytopenia
  • Antibodies against the human platelet antigen PlA1 are detected in most individuals with PTP
  • Patients with PTP almost universally are either multiparous women or persons 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) which should be administered as soon as the diagnosis is suspected
  • Platelets are not indicated unless severe bleeding is present, but if they are to be administered, HLA-matched platelets are preferred
  • A second course or IVIG, plasma exchange, corticosteroids, or splenectomy may be used in case of refractoriness
  • PlA1-negative or washed blood products are preferred for subsequent transfusions
• Pregnancy (see Pregnancy, [[Pregnancy]]): 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
  • Platelet counts < 100,000/mcL, however, are observed in < 10% of pregnant women in the third trimester; decreases to < 70,000/mcL should prompt consideration of pregnancy-related ITP (see above) as well as preeclampsia or a pregnancy-related thrombotic microangiopathy

Unknown/Other Mechanism

• Bumetanide (Bumex): rare reports of thrombocytopenia
• Sepsis (see Sepsis, [[Sepsis]])
  • Physiology: multiple mechanisms have been implicated
    • Consumptive Coagulopathy: related to sepsis-induced platelet activation with/without frank disseminated intravascular coagulation (DIC)
    • Hemodilution: associated with intravenous fluid resuscitation
    • Increased Circulating Histones (JAMA, 2016) [MEDLINE]
    • Platelet Sequestration

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, [[Complete Blood Count]])

• Thrombocytopenia

Peripheral Blood Smear (see xxxx, [[xxxx]])

• Check fro Platelet Clumping

Clinical Locations of Hemorrhage

• Central Nervous System Hemorrhage: central nervous system hemorrhage is the major cause of bleeding-related deaths in patients with severe congenital factor deficiencies
  • Intracerebral Hemorrhage (see Intracerebral Hemorrhage, [[Intracerebral Hemorrhage]])
  • Subarachnoid Hemorrhage (SAH) (see Subarachnoid Hemorrhage, [[Subarachnoid Hemorrhage]])
  • Subdural Hematoma (SDH) (see Subdural Hematoma, [[Subdural Hematoma]])
• Epistaxis (see Epistaxis, [[Epistaxis]])
  • Hereditary Hemorrhagic Telangiectasia (see Hereditary Hemorrhagic Telangiectasia, [[Hereditary Hemorrhagic Telangiectasia]]): epistaxis is a common symptom
  • Von Willebrand Disease (see Von Willebrand Disease, [[Von Willebrand Disease]]): epistaxis is a common symptom in young males
• Excessive Menstrual Bleeding
  • Menorrhagia (see Menorrhagia, [[Menorrhagia]]): loss of >80 mL of blood per cycle (or >4 super pads or tampons per day) or menses lasting >7 days
• Gastrointestinal Hemorrhage (see Gastrointestinal Hemorrhage, [[Gastrointestinal Hemorrhage]]): gastrointestinal hemorrhage in presence of a bleeding disorder is usually associated with underlying gastrointestinal tract pathology
  • Von Willebrand Disease (Especially Types 2 and 3): has been associated with angiodysplasia of the bowel and gastrointestinal hemorrhage
• Hemarthrosis (see Hemarthrosis, [[Hemarthrosis]])
  • Moderate-Severe Factor II/Prothrombin Deficiency (see Prothrombin Deficiency, [[Prothrombin Deficiency]])
  • Moderate-Severe Factor V Deficiency (see Factor V Deficiency, [[Factor V Deficiency]])
  • Moderate-Severe Factor VII Deficiency (see Factor VII Deficiency, [[Factor VII Deficiency]])
  • Moderate-Severe Congenital Factor VIII Deficiency (Hemophilia A) (see Hemophilia A, [[Hemophilia A]])
  • Moderate-Severe Factor IX Deficiency (Hemophilia B) (see Hemophilia B, [[Hemophilia B]])
  • Moderate-Severe Factor X Deficiency (see Factor X Deficiency, [[Factor X Deficiency]])
  • Moderate-Severe Fibrinogen Deficiency (see Afibrinogenemia, [[Afibrinogenemia]])
  • Von Willebrand Disease (see Von Willebrand Disease, [[Von Willebrand Disease]]): with factor VIII levels <5%
• Hematuria (see Hematuria, [[Hematuria]]): hematuria in presence of a bleeding disorder is usually associated with underlying urinary tract pathology
• Hemoperitoneum (see Hemoperitoneum, [[Hemoperitoneum]]): has been reported in association with rupture of ovarian cysts in association with a bleeding disorder
• Mucosal/Gingival Bleeding
  • Platelet Adhesion Defect: may have increased bleeding after dental cleanings or gum manipulation
• Muscle Hematoma
  • Anti-Factor VIII Antibody (see Anti-Factor VIII Antibody, [[Anti-Factor VIII Antibody]]): common
  • Moderate-Severe Factor II/Prothrombin Deficiency (see Prothrombin Deficiency, [[Prothrombin Deficiency]])
  • Moderate-Severe Factor V Deficiency (see Factor V Deficiency, [[Factor V Deficiency]])
  • Moderate-Severe Factor VII Deficiency (see Factor VII Deficiency, [[Factor VII Deficiency]])
  • Moderate-Severe Congenital Factor VIII Deficiency (Hemophilia A) (see Hemophilia A, [[Hemophilia A]])
  • Moderate-Severe Factor IX Deficiency (Hemophilia B) (see Hemophilia B, [[Hemophilia B]])
  • Moderate-Severe Factor X Deficiency (see Factor X Deficiency, [[Factor X Deficiency]])
  • Moderate-Severe Fibrinogen Deficiency (see Afibrinogenemia, [[Afibrinogenemia]])
• Post-Partum Hemorrhage
  • Common in women with underlying bleeding disorders
  • In women with type 1 Von Willebrand Disease and symptomatic hemophilia carriers in whom levels of Von Willebrand factor and factor VIII usually normalize during pregnancy, the onset of post-partum hemorrhage may be delayed
  • Women with a history of postpartum hemorrhage have a high risk of recurrence with subsequent pregnancies
• Retroperitoneal Hemorrhage (see Retroperitoneal Hemorrhage, [[Retroperitoneal Hemorrhage]])
• Surgical Bleeding
  • Post-Colonoscopic Polypectomy (see Colonoscopy, [[Colonoscopy]]): delayed bleeding may occur
  • Post-Tonsillectomy (see Tonsillectomy, [[Tonsillectomy]]): Bleeding may occur early after surgery or after approximately 7 days postoperatively (with loss of the eschar at the surgical site)

Clinical Patterns of Bleeding

Clinical Manifestations

Hemorrhagic Manifestations

• xxx

• The incidence of bleeding increases as platelet counts decrease below 10,000/!L. In two recent studies, the use of smaller doses of platelet concentrates resulted in a greater number of transfusions being required. The incidence of significant bleeding was greater with lower dose transfusion in one study, and not different in the other study. Current studies are addressing the issue of prophylactic versus therapeutic transfusions in patients with platelet counts less than 10,000/μL. Alloimmunization is decreased by the use of leukocyte-reduced platelets. Post- transfusion increments in platelet count decrease as the number of units transfused increases because of the development of alloimmunization. ABO incompatibility decreases the increment in platelet count post transfusion.

Treatment

Platelet Transfusion (see Platelet Transfusion, [[Platelet Transfusion]])

• xxx

References

• Dose of prophylactic platelet transfusions and the prevention of hemorrhage. N Engl J Med 2010; 362:600-613.
• A randomized controlled trial comparing standard- and low-dose strategies for transfusion of platelets (SToP) to patients with thrombocytopenia. Blood 2009; 113:1564-1573.
• Evidence-based platelet transfusion guidelines. Hematology Am Soc Hematol Educ Program 2007:172- 178
• Pseudothrombocytopenia after abciximab (Reopro) treatment. Circulation 1999; 100:1460
• Thrombocytopenia complicating treatment with intravenous IIb/IIIa receptor inhibitors: a pooled analysis. Am Heart J 2000; 140:206-211
• Histone-Associated Thrombocytopenia in Patients Who Are Critically Ill. JAMA. 2016;315(8):817-819. doi:10.1001/jama.2016.0136 [MEDLINE]