Severe vitamin B12 deficiency may present with hematologic abnormalities that mimic thrombotic microangiopathy disorders such as hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Shravya Govindappagari et al report a patient diagnosed with severe vitamin B12 deficiency, following termination of pregnancy for suspected preeclampsia and HELLP syndrome at 21 weeks' gestation. When hemolysis and thrombocytopenia persisted after delivery, testing was performed to rule out other etiologies of thrombotic microangiopathy, including atypical hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and vitamin B12 deficiency. This work-up revealed undetectable vitamin B12 levels and the presence of intrinsic factor antibodies, consistent with pernicious anemia. Parenteral B12 supplementation was initiated, with subsequent improvement in hematologic parameters. This case emphasizes the importance of screening for B12 deficiency in pregnancy, especially in at-risk women with unexplained anemia or thrombocytopenia. Moreover, providers should consider B12 deficiency and pernicious anemia in the differential diagnosis of pregnancy-associated thrombotic microangiopathy.
A 40-year-old multiparous African American woman at 21 weeks' 4-day gestation, with known chronic hypertension, was transferred to our medical center for management of the hypertensive emergency. Prior to transfer, the patient had marked blood pressure elevation (peak 192/129 mmHg) and laboratory evaluation notable for hemoglobin 11.0 g/dl, platelet count 66 k/μl, alanine transaminase (ALT) 20 U/L, aspartate transaminase (AST) 40 U/L, and creatinine 0.7 mg/dl. Urine dipstick detected 4+ protein, 4+ blood, and +nitrites, and urine drug screen was positive for methamphetamines and marijuana. Intravenous ceftriaxone was given empirically for urinary tract infection.
On arrival to our medical center, blood pressure peaked at 205/114 mmHg and laboratory findings were like those noted above. In addition, lactate dehydrogenase (LDH) level was 985 U/L, with haptoglobin <8 mg/dl and 3 schistocytes per high power field on peripheral smear. Urine protein/creatinine ratio was 2.61 mg/mg (normal <0.3 mg/mg). Estimated fetal weight by ultrasound was 451g, which was appropriate for her gestational age. We suspect that methamphetamine use precipitated her hypertensive crisis, but the clinical picture and laboratory findings were concerning for severe preeclampsia and HELLP syndrome. Due to her previable gestational age and the life-threatening nature of her condition, termination of pregnancy was recommended, and she agreed. Magnesium sulfate was initiated for seizure prophylaxis, and she was managed in the intensive care unit on an intravenous nicardipine drip. Within 12 hours of her first misoprostol dose for labor induction, she had a precipitous vaginal delivery of a nonviable female neonate. Pathology examination of the placenta revealed decidual arteriopathy and accelerated villous maturation, which are findings reflective of severe hypertension and placental hypoxia.
Following delivery, severe hypertension (≥160/110 mmHg) persisted throughout the postpartum period despite triple agent antihypertensive therapy. On postpartum day 5, she continued to have severe range blood pressures, but declined inpatient stay and was discharged home on an oral regimen of chlorthalidone (50mg daily), amlodipine (10mg daily), and telmisartan (80mg daily). During her postpartum course in the hospital, the patient had a workup for secondary causes of hypertension. She had maternal echo showing mild left ventricular hypertrophy, but normal left ventricular ejection fraction (69%) and no evidence of aortic coarctation. She had normal renal artery Dopplers, ruling out renal artery stenosis. Serum aldosterone/renin ratio was normal, ruling out primary aldosteronism. She did not complete a 24-hour urine collection to measure total metanephrines and therefore pheochromocytoma was not formally ruled out. We suspect that methamphetamine use precipitated her hypertensive emergency, but blood pressures remained severe despite 7 days of inpatient observation and drug cessation.
TMA also persisted despite termination of pregnancy and drug cessation. On postpartum day 1 laboratory values were as follows: hemoglobin 8.4 g/dl, platelet count 90 k/μl, LDH 706 U/L, haptoglobin <8 mg/dl, 2-3 schistocytes per high power field on smear, and reticulocyte count 4.6% (normal 0.5-2.0%). Her reticulocyte production index was noted to be suboptimal at 2.1% (normal >3.0%), after adjustment for low hematocrit (30.5%) . Considering that the patient's liver enzymes remained normal after delivery despite ongoing hemolysis and thrombocytopenia, the diagnosis of HELLP syndrome was questioned. Alternative TMA etiologies were considered, including aHUS, TTP, and vitamin B12 deficiency. Serum creatinine peaked at 0.9 mg/dl and aHUS genetic panel was negative for disease-associated complement gene variants (Machaon Diagnostics), making a diagnosis of aHUS less likely. ADAMTS13 activity was 75% (normal >67%), making a diagnosis of TTP less likely. Meanwhile, vitamin B12 level was undetectable <146 ρg/ml (normal 213-816 ρg/ml) and intrinsic factor blocking antibodies were positive, consistent with pernicious anemia. Mean corpuscular volume was paradoxically low at 75.3 FL (normal 80-100 FL), and other causes of anemia were ruled out with normal iron panel, hemoglobin electrophoresis, and folate level.
Following the diagnosis of pernicious anemia, the patient was started on subcutaneous B12 injections at a dose of 1000 mcg daily. She received 5 injections of vitamin B12 during her postpartum hospital stay. While blood pressures remained severely elevated on the day of discharge (postpartum day 5), laboratory parameters showed signs of improvement: Hemoglobin 9.5 g/dl, platelet count 175 k/μl, and LDH 404 U/L. The patient was discharged home with a plan for continued B12 supplementation and close outpatient follow up. At 2 weeks postpartum the patient had normal blood pressure (127/82) and was clinically well, but she declined additional laboratory testing.