What are the possible causes of thrombocytopenia (low platelet count) in a pregnant woman, not taking any medications, with no prior medical history?

Causes of Thrombocytopenia in Pregnancy

Gestational thrombocytopenia is by far the most common cause, accounting for approximately 75% of all cases of thrombocytopenia in pregnancy, followed by hypertensive disorders of pregnancy (preeclampsia/HELLP syndrome) which account for most of the remaining 25%, while immune thrombocytopenia (ITP) is relatively uncommon. 1

Primary Causes by Frequency

Gestational Thrombocytopenia (Most Common - ~75% of cases)

• Occurs in approximately 5-10% of all pregnancies and represents the benign majority of pregnancy-associated thrombocytopenia 1, 2, 3
• Characterized by five key features: (1) asymptomatic, mild thrombocytopenia, (2) no history of thrombocytopenia when not pregnant (except possibly during previous pregnancy), (3) occurs during late gestation (third trimester), (4) not associated with fetal thrombocytopenia, and (5) resolves spontaneously after delivery 1, 4
• Platelet counts typically remain >70,000/μL, with approximately two-thirds falling between 130,000-150,000/μL 1, 4
• Mechanism involves hemodilution combined with increased platelet activation and clearance during normal pregnancy 1, 5

Hypertensive Disorders of Pregnancy (~20-25% of cases)

• Preeclampsia occurs in approximately 10% of pregnancies, with thrombocytopenia developing in up to 25% of these patients 1
• HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) accounts for a significant portion of the remaining cases after gestational thrombocytopenia 1, 3, 6
• These conditions predominantly occur in the third trimester, making timing a critical diagnostic clue 5
• Severe preeclampsia can rarely occur in the first trimester and may progress to DIC 7

Immune Thrombocytopenia (ITP) (Relatively Uncommon)

• Estimated to occur in 1 in 1,000 to 1 in 10,000 pregnant women, making it a relatively uncommon cause 1
• Critical distinguishing features from gestational thrombocytopenia: (1) history of thrombocytopenia when not pregnant, (2) may occur early in first or second trimester, (3) typically more severe platelet counts, and (4) may be associated with fetal/neonatal thrombocytopenia 1, 4, 3
• Women with previously diagnosed ITP may experience exacerbation or relapse during pregnancy 1

Timing as a Diagnostic Algorithm

First or Second Trimester Thrombocytopenia

When thrombocytopenia presents early in pregnancy, this strongly suggests ITP or other pathology rather than gestational thrombocytopenia 4

Consider these specific causes:

• Immune thrombocytopenia (ITP) - may appear early in first trimester 6
• Thrombotic thrombocytopenic purpura (TTP) - thrombocytopenia with microangiopathic hemolytic anemia in first trimester should raise high suspicion; ADAMTS13 activity testing should be obtained immediately 5
• Disseminated intravascular coagulation (DIC) - particularly with septic abortion, which can progress to death within 18 hours 7
• Hereditary thrombocytopenia or pre-existing conditions 3

Third Trimester Thrombocytopenia

Late-onset thrombocytopenia strongly suggests gestational thrombocytopenia or hypertensive disorders 4

Primary considerations:

• Gestational thrombocytopenia - benign, mild, asymptomatic 1, 4
• Preeclampsia/HELLP syndrome - look for hypertension, proteinuria, elevated liver enzymes, hemolysis 1, 3
• Acute fatty liver of pregnancy - rare but life-threatening 1, 3

Additional Causes to Exclude

Thrombotic Microangiopathies

• Thrombotic thrombocytopenic purpura (TTP) - characterized by thrombocytopenia, microangiopathic hemolytic anemia, neurologic symptoms, renal dysfunction, and fever 5, 3
• Atypical hemolytic uremic syndrome - similar presentation to TTP 3

Obstetric Emergencies

• Disseminated intravascular coagulation (DIC) - associated with septic abortion, amniotic fluid embolism, intrauterine fetal death, or massive obstetric hemorrhage 1, 7, 3
• Amniotic fluid embolism - can occur during first-trimester termination or amniocentesis, presenting with anxiety, mental status changes, and rapid cardiovascular collapse 7

Other Medical Conditions

• Antiphospholipid antibody syndrome - should be considered in the differential 1, 3
• Folate deficiency - more common in pregnancy due to increased demands 1
• Hereditary thrombocytopenia - may be unmasked during pregnancy 3

Critical Diagnostic Pitfall

ITP cannot be distinguished from gestational thrombocytopenia with certainty because both diagnoses are based on exclusion of other causes 1. The diagnosis rests largely on:

• Severity of thrombocytopenia (gestational typically >70,000/μL) 1, 4
• Timing during gestation (gestational occurs late, ITP can occur early) 4
• History of prior thrombocytopenia when not pregnant (strongly suggests ITP) 1, 4

A thorough history is paramount - evidence of previous thrombocytopenia at a time when the patient was not pregnant strongly suggests ITP rather than gestational thrombocytopenia 1, 4