This document provides an overview of thrombocytopenia, including its definition, clinical significance, etiology, mechanisms, clinical approach, and initial workup. Thrombocytopenia is defined as a platelet count below 150 x 109/L and can be caused by decreased platelet production, increased platelet destruction, or platelet sequestration. A thorough history, physical exam, and initial lab workup including CBC, liver/renal function, coagulation profile, and infectious/autoimmune screening help determine the underlying etiology and guide further management.

1. CLINICAL APPROACH TO
THROMBOCYTOPENIA
Dr/ Marwa Mahmoud Khalifa
MD PHD Internal Medicine & Hematology

2. THROMBOCYTOPENIA
 Thrombocytopenia is defined as a platelet count
below 150 x 109/L as the lower limit of normal.
 However, platelet counts between 100 and 150
109/L do not necessarily indicate disease if they
have been stable for more than 6 months.

3. THROMBOCYTOPENIA
Clinically significant spontaneous bleeding does not
usually occur until the platelet count is less than 10-
20 x 109/L.
However, the presence of thrombocytopenia can
aggravate surgical or traumatic bleeding or prevent
the administration of effective treatment for several
conditions (eg, antiviral therapy for chronic hepatitis C
virus infection or cancer chemotherapy, elective
surgery)

4. ETIOLOGY
 Primary immune thrombocytopenia (primary ITP).
 Drug-induced immune thrombocytopenia:
 Heparin-induced thrombocytopenia (HIT) - in this condition, anti-platelet
antibodies activate platelets resulting in thrombosis (both arterial and
venous)
 Quinine
 Sulfonamides, ampicillin, vancomycin, piperacillin
 Acetaminophen, ibuprofen, naproxen
 Cimetidine
 Glycoprotein IIb/IIIa inhibitors
 Other over the counter remedies, supplements, foods like African bean,
sesame seeds, walnuts) and beverages (herbal teas and cranberry juice)
 Drug-induced non-immune thrombocytopenia. Drugs like valproic
acid, daptomycin, linezolid cause thrombocytopenia by dose-
dependent suppression of platelet production.

5.  Infections:
 Viral: HIV, hepatitis C, Ebstein-Barr virus, parvovirus, mumps, varicella, rubella,
Zika viral infections
 Sepsis causes bone marrow suppression.
 Helicobacter pylori
 Leptospirosis, brucellosis, anaplasmosis, and other tick-borne infections
 Malaria, babesiosis intracellular parasite infections are associated with
thrombocytopenia and hemolytic anemia
 Hypersplenism due to chronic liver disease
 Chronic alcohol abuse
 Nutrient deficiencies (folate, vitamin B12, copper)
 Autoimmune disorders like SLE, RA associated with secondary ITP
 Pregnancy. Mild thrombocytopenia presents in gestational
thrombocytopenia; moderate-severe thrombocytopenia can occur in
preeclampsia and HELLP (hemolysis, elevated liver enzymes, low
platelet count) syndrome

6.  Myelodysplasia
 Malignancy: cancer with chronic DIC, cancer with marrow
suppression (leukemia, lymphoma, solid tumors)
 Paroxysmal nocturnal hemoglobinuria (PNH)
 Thrombotic microangiopathy (TMA)
 Thrombotic thrombocytopenic purpura (TTP), a condition
manifested by fever, renal failure, thrombocytopenia,
microangiopathic hemolytic anemia with or without neurologic
manifestations
 A hemolytic uremic syndrome (HUS) caused by Shiga toxin-
producing organism (E. coli and Shigella), seen in children.
 Drug-induced TMA: quinine, specific chemotherapy agents
 Antiphospholipid antibody syndrome
 Aplastic anemia
 Inherited thrombocytopenia. Often seen in children, rare in
adults

7. MECHANISMS OF THROMBOCYTOPENIA
 Decreased production :BM failure (AA, MDS, CIT)
 Increased destruction of platelets: (DIC, TMAs)
 Platelet sequestration: congestive splenomegaly
 Hemodilution: massive transfusions
 Combined (ITP, HCV induced)

8. CLINICAL APPROACH
 History taking : autoimmune disorders, infections,
or malignancies; pregnancy; recent medications
(heparin, antibiotics, antiviral) and vaccinations;
recent travels (eg, malaria, rickettsiosis, dengue
fever); recent transfusions; recent organ
transplantation; and risk factors for retroviral
infections and viral hepatitis.

9. Physical examination
 organomegaly / lymphadenopathy
 Mucocutaneous bleeding.
 joint or extensive soft tissue bleeding 
coagulation abnormalities, such as occurs in DIC.
 ischemic limb and skin necrosis HIT.

10. IX:
 CBC film
 Liver, renal functions
 Coagulation profile, D dimer
 ESR, CRP, LDH
 Virology (HBV, HCV, HIV)
 Autoimmune profile (ANA, anti ds DNA)
 H pyloi ( fecal antigen, UBT)
 BMA+/- biopsy
 US abdomen, CXR
 Antiplatelet Ab
 Direct antiglobulin test