Decreased platelet production (problem with production in the bone marrow)
MOA: Hypocellular bone marrow vs. Hypercellular bone marrow vs. Marrow replacement vs. Bone marrow suppression
Bone marrow failure (e.g., aplastic anemia, paroxysmal nocturnal hemoglobinuria, Shwachman-Diamond syndrome)
Bone marrow suppression (e.g. drugs (Linezolid, Daptomycin), chemotherapy, or irradiation)
Chronic alcohol abuse
Infections (cause bone marrow suppression): Viral infections (CMV, EBV, HCV, HIV, HSV, VZV), mumps, parvovirus B19, rickettsia, rubella
Myelodysplastic syndrome
Myeloproliferative syndromes
Leukemia
Myelofibrosis, other infiltrative processes.
Neoplastic marrow infiltration; Hematologic malignancies; solid malignancies
Severe megaloblastic anemia from nutritional deficiencies (vitamin B12 and folate)
Congenital macrothrombocytopenias (e.g., Alport syndrome, Bernard-Soulier syndrome, Fanconi anemia, platelet-type or pseudo–von Willebrand disease, Wiskott-Aldrich syndrome)
Increased platelet Destruction / Consumption  (Platelets being used up too fast or destroyed)
MOA: Immune-mediated vs. non-immune mediated.
Immune-mediated (primary vs. secondary)
Primary: Immune thrombocytopenic purpura
Secondary:
Alloimmune destruction (e.g., posttransfusion, neonatal, posttransplantation)
Autoimmune syndromes (e.g., antiphospholipid syndrome(APS), systemic lupus erythematosus (SLE), sarcoidosis)
Infection (immune-mediated): Viral infections (CMV, EBV, HCV, HIV, HSV, VZV), mumps, parvovirus B19, rickettsia, rubella
Lymphoproliferative (CLL, lymphoma)
Drug-induced thrombocytopenia: Heparin (HIT), Ranitidine, vancomycin, alcohol, cephalosporins, thiazides, sulfonamides, Bactrim, MMR vaccine, etc.
Non-immune-mediated
MAHA (DIC, HUS, TTP)
-Disseminated intravascular coagulation
-Hemolytic uremic syndrome
-Thrombotic thrombocytopenic purpura
Severe sepsis
Vasculitis
Cavernous hemangioma
Mechanical destruction: aortic valve, mechanical valve, cardiopulmonary bypass, continuous venovenous hemofiltration (CVVH), intra-aortic balloon pump (IABP)
Preeclampsia/HELLP syndrome
Splenic sequestration/Abnormal Distribution/Other
Splenic sequestration; Hypersplenism (e.g., distributional thrombocytopenia)
Dilutional thrombocytopenia (e.g., hemorrhage, excessive crystalloid infusion)
Gestational thrombocytopenia
Liver disease (e.g., cirrhosis, fibrosis, portal hypertension)
Pseudothrombocytopenia
Pulmonary emboli
Pulmonary hypertension
Ehrlichiosis/anaplasmosis
Babesiosis
Rocky Moutain Spotted Fever

Thinking through the Differential Diagnosis

Thrombocytopenia = low platelets
Causes of low platelets
Not making enough. Problems with production in bone marrow.
-Platelets are being used too fast that their number is low in blood e.g. increased platelet turnover during sepsis
-Platelets are dying too early (i.e are being destroyed) e.g. platelet binding antibodies cause low platelets by increasing platelet clearance.
-Platelets are being sequestered (e.g. in the spleen) or diluted.

Thrombocytopenia is usually acquired. Repeat lab to r/o lab error. In patients with splenomegaly, platelets are trapped by the spleen.
In regard to low platelet counts, only clinical bleeding and not platelet count numbers should be treated. Treatment should focus on the underlying disease.
DIC = Disseminated intravascular coagulation. HUS = Hemolytic uremic syndrome; TTP = Thrombotic thrombocytopenic purpura

References / Further Reading
Internist (Berl). 2010 Nov;51(11):1397-410. Differential diagnosis and treatment of thrombocytopenia. https://www.ncbi.nlm.nih.gov/pubmed/20941473
Am Fam Physician 2012;85(6):612-622. Thrombocytopenia. https://www.aafp.org/afp/2012/0315/p612.html
https://www.consultant360.com/content/thrombocytopenia-how-best-determine-cause Last Accessed Mar 2018
Am Fam Physician 2011;83(6):719-724. Transfusion of Blood and Blood Products: Indications and Complications.
F1000Prime Reports. 2014;6:45. Management of thrombocytopenia. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047949/

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