Thrombotic thrombocytopenic purpura during pregnancy and its overlap with the HELLP syndrome, a clinical dilemma: A case report and review of the literature :Mafdy Basta, Journal of Obstetric Anaesthesia and Critical Care

CASE REPORT
Year : 2019 | Volume : 9 | Issue : 1 | Page : 50--52

Thrombotic thrombocytopenic purpura during pregnancy and its overlap with the HELLP syndrome, a clinical dilemma: A case report and review of the literature

Mafdy Basta
Department of Anesthesiology and Perioperative Medicine, Augusta University, GA, USA

Correspondence Address:
Dr. Mafdy Basta
Department of Anesthesiology, Medical College of Georgia at Augusta University, 1120 15th St., Augusta, GA - 30912
USA

Abstract

Thrombotic thrombocytopenic purpura (TTP), when occurs during pregnancy, displays findings that could overlap with preeclampsia, especially the HELLP (Hemolysis, Elevated Liver tests, Low Platelets) syndrome. The following presentation is a case report that describes TTP in a pregnant patient whose pregnancy was also complicated by preeclampsia and illustrates some features that could help differentiate and manage this clinical dilemma.

How to cite this article:
Basta M. Thrombotic thrombocytopenic purpura during pregnancy and its overlap with the HELLP syndrome, a clinical dilemma: A case report and review of the literature.J Obstet Anaesth Crit Care 2019;9:50-52

How to cite this URL:
Basta M. Thrombotic thrombocytopenic purpura during pregnancy and its overlap with the HELLP syndrome, a clinical dilemma: A case report and review of the literature. J Obstet Anaesth Crit Care [serial online] 2019 [cited 2023 Mar 27 ];9:50-52
Available from: https://www.joacc.com/text.asp?2019/9/1/50/255889

Full Text

Case Report

A 39-year-old African American female, gravida 11 para 7, presented to the emergency department at 25 weeks gestation with headache, nausea, and vomiting. Past medical history was significant for thrombotic thrombocytopenic purpura (TTP), pulmonary embolism, and hypertension.

Her most recent episode of TTP took place 1 year prior, at 25 weeks gestation, was associated with severe preeclampsia and managed with a few sessions of plasmapheresis. Due to fetal distress, an emergency cesarean section (CS) was performed. Unfortunately, neonatal demise eventually took place shortly after birth.

On examination, the patient's blood pressure was 150/90 and urine protein >300 mg/dl. Pertinent laboratory findings included severe thrombocytopenia (7,000/mm3), hemoglobin 8.6 g/dl, and slight schistocytes on peripheral smear. Reticulocyte count 4.9% (upper limit of normal 2%). Haptoglobin <1 mg/dl (lower limit of normal 40 mg/dl); lactate dehydrogenase (LDH) 1077 U/L (upper limit of normal 246 U/L); and total bilirubin 4.4 mg/dl with direct bilirubin 1.1 mg/dl. Levels of transaminases, blood urea nitrogen (BUN), and serum creatinine (Cr) are within normal limits. D-dimer level was 1,958 ng/ml (upper limit of normal 230 ng/ml); prothrombin time (PT), activated partial thromboplastin time (aPTT), and international normalized ration (INR) all are within normal limits.

Review of the patient's old records revealed ADAMTS13 (A Disintegrin And Metallo-proteinase with Thrombospondin type 1 motif, member 13) level at 14% with positive ADAMTS13 inhibitor screen (Bethseda titer 2.7), both obtained about 6 weeks prior to current admission, as part of workup for an episode of TTP.

As her previous episodes of TTP correlated with pregnancy, a presumptive diagnosis of acquired TTP was made. However, preeclampsia with severe features/HELLP (Hemolysis, Elevated Liver tests, Low Platelets) syndrome, superimposed on hypertension, could not be excluded as contributing to her thrombotic microangiopathy (TMA).

Hospital Course

Following haematology consultation, patient underwent daily plasmapheresis with fresh frozen plasma (FFP) resulting in rapid improvement of the platelet count, having reached at 180,000/mm3 on hospital admission day 7, at which time the plasma exchange was stopped. However, platelet count started to decrease again and did not respond to reinstating plasmapheresis; counts as low as 11,000/mm3 were reported over the following 48 h. Due to refractory thrombocytopenia, and possible contribution from HELLP syndrome, the decision was made to proceed with emergent CS, which was performed under general anesthesia. Platelet transfusions were used perioperatively in anticipation of bleeding.

Postpartum and due to refractory thrombocytopenia, twice a day plasmapheresis along with increasing volume (4-5 l) was used. Concurrently, pulse dose (1 g daily × 3 days) IV methylprednisolone followed by oral prednisone 60 mg daily was added till thrombocytopenia resolved. Plasmapheresis was continued till sustained (>3 consecutive days) platelet counts >150,000/mm3 were obtained. A total of 22 plasmapheresis sessions were used during the hospital course.

Repeat ADAMTS13 activity level was 9% along with positive inhibitor screen. Due to ADAMTS13 level <10%, the patient was started on rituximab to decrease relapses. She was discharged home and instructed to follow up with the haematology clinic as scheduled.

Discussion

TMAs include a number of conditions in which platelet microthrombi form in small vessels and lead to organ damage. The hall marks of TMA are microangiopathic hemolytic anemia (MAHA), which is inferred from the presence of schistocytes on a peripheral blood smear and biochemical evidence of hemolysis, and thrombocytopenia, which could be severe.[1]

TTP, the prototype of TMA, is a severe, life-threatening disease that needs urgent diagnosis and prompt therapeutic intervention. TTP may complicate the course of pregnancy and create a vital risk for both mother and child. Differential diagnosis with other obstetric and medical disorders may be difficult due to the overlap of several clinical and laboratory findings.[2]

Pregnancy seems to increase the risk of relapses and the severity of episodes of TTP which can occur during any trimester or postpartum.[3]

TTP is associated with severely reduced activity of ADAMTS13, a protease that cleaves newly synthesised ultra large multimers of von Willebrand factor (vWF) on endothelial cells into a smaller form that can circulate. Presumably, when ADAMTS13 is inhibited in TTP, the ultra large multimers can spontaneously aggregate platelets leading to the clinical syndrome of TTP.[4]

ADAMTS13 may be reduced because of a neutralising autoantibody (acquired TTP) or an inherited mutation of ADAMTS13 gene (hereditary TTP).[5]

TTP should be suspected when any patient presents with thrombocytopenia and MAHA; end-organ damage, mostly manifesting as renal insufficiency or neurologic phenomena (seizures, strokes), and fever also may occur, although the minority of patients with TTP present with all of the aforementioned features.[6],[7]

The diagnosis of TTP relies primarily on a through clinical assessment, since ADAMST13 activity is often not immediately available. LDH is usually significantly elevated and has a diagnostic and prognostic value in TTP.[8] Finding very low levels (<10%) of ADAMTS13 may also be a negative prognostic factor.[9] The findings of thrombocytopenia with a relative normal prothrombin time help eliminate disseminated intravascular coagulopathy (DIC) from the differential.[10]

Differential diagnoses during pregnancy include other conditions that present with MAHA, including preeclampsia with severe features, the HELLP syndrome, and DIC.

The HELLP syndrome describes a variant of preeclampsia that classically occurs after 28 weeks of gestation in a patient suffering from preeclampsia. Moreover, HELLP can overlap with or present concurrently with TTP and create diagnostic challenges.[11] It can progress to liver failure and deaths are also reported due to hepatic rupture. In severe cases, elevated D-dimers consistent with DIC are also found. Delivery of the fetus will most often result in cessation of the HELLP syndrome. About a quarter of women who suffer from the HELLP will have a recurrence with a later pregnancy.[12]

In DIC, prolonged PT and aPTT, low fibrinogen, and elevated D-dimer are typically present.

The clinical course of TTP is not affected by delivery. The most important treatment is urgent plasma exchange which removes the autoantibody to ADAMTS13 and supplies functional ADAMTS13 in the replacement plasma. Platelet transfusion should be reserved for treatment of severe bleeding due to the potential increased risk of thrombosis, but platelets should not be withheld in a bleeding patient due to this concern.[3]

Untreated TTP is rapidly fatal. Mortality in the pre-plasma exchange era was more than 90%. Currently, plasma exchange therapy is the cornerstone of TTP treatment and has reduced mortality to less than 20%.[13]

Glucocorticoid therapy, either prednisone 1 mg per kg daily orally or, for more severe disease, methylprednisolone 125 mg IV 2-4 times daily, is also added to patients presumed to have TTP. The glucocorticoid is continued until the patient has fully recovered and then tapered over 1-2 weeks. Glucocorticoids are thought to reduce production of the ADAMTS13 inhibitor (autoantibody) by mechanisms similar to those in other autoimmune diseases.[7]

Plasma infusion may be used as a temporizing measure, but plasma exchange has been shown to be superior to simple plasma infusion in therapy of acquired TTP.[14] This may be due to removal of inhibitory antibodies in addition to supplying large amounts of ADAMTS13.

One estimated plasma volume (approximately 40 ml/kg body weight) is recommended to be exchanged at each procedure. Plasma exchange should be continued daily until platelets count of >150,000/mm3 is sustained for three consecutive days and LDH has normalized at which point the exchange can be stopped. If the platelet count falls or LDH level rises again, daily exchange should be reinstated.[15]

There is increasing evidence that the use of the anti-CD20 therapy, rituximab, may reduce the incidence of relapses and shorten the duration of therapy in refractory disease.[16]

Conclusion

When TTP is suspected during pregnancy, plasma exchange therapy should be performed without delay and monitored with platelet count and LDH level. Delivery of the fetus should be considered if thrombocytopenia persists (or recurs after initial improvement) despite repeated plasma exchange, as concurrent HELLP could be the culprit for the clinical presentation, and differentiating TTP from coexisting HELLP syndrome could be difficult in those cases.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Patient's written consent for publication was obtained at the time of hospital admission.

References

1	McMinn JR, George JN. Evaluation of women with clinically suspected thrombotic thrombocytopenic purpura-hemolytic uremic syndrome during pregnancy. J Clin Apher 2001;16:202.
2	Savignano C, Rinaldi C, De Angelis V. Pregnancy associated thrombotic thrombocytopenic purpura: Practical issues for patient management. Transfus Apher Sci 2015;53:262-8.
3	Scully M, Thomas M, Underwood M, Watson H, Langley K, Camilleri RS, et al. Thrombotic thrombocytopenic purpura and pregnancy: Presentation, management, and subsequent pregnancy outcomes. Blood 2014;124:211-9.
4	Peyvandi F, Ferrari S, Lavoretano S, Canciani MT, Mannucci PM. von Willebrand factor cleaving protease (ADAMTS-13) and ADAMTS-13 neutralizing autoantibodies in 100 patients with thrombotic thrombocytopenic purpura. Br J Haematol 2004;127:433-9.
5	Sadler JE. Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura. Blood 2008;112:11-8.
6	George JN, Nester CM. Syndromes of thrombotic microangiopathy. N Engl J Med 2014;371:654.
7	Scully M, Hunt BJ, Benjamin S, Liesner R, Rose P, Peyvandi F, et al. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol 2012; 158:323.
8	Patton JF, Manning KR, Case D, Owen J. Serum lactate dehydrogenase and platelet count predict survival in thrombotic thrombocytopenic purpura. Am J Hematol 1994;47:94-9.
9	Coppo P, Wolf M, Veyradier A, Bussel A, Malot S, Millot GA, et al. Prognostic value of inhibitory anti-ADAMTS13 antibodies in adult-acquired thrombotic thrombocytopenic purpura. Br J Haematol 2006;132:66-74.
10	Park YA, Waldrum MR, Marques MB. Platelet count and prothrombin time help distinguish thrombotic thrombocytopenic purpura-hemolytic uremic syndrome from disseminated intravascular coagulation in adults. Am J Clin Pathol 2010;133:460-5.
11	Sibai BM. Imitators of severe preeclampsia. Obstet Gynecol 2007;109:956-66.
12	Baxter JK, Weinstein L. HELLP syndrome: The state of the art. Obstet Gynecol Surv 2004;59:838-45.
13	von Baeyer H. Plasmapheresis in thrombotic microangiopathy-associated syndromes: Review of outcome data derived from clinical trials and open studies. Ther Apher 2002;6:320.
14	Rock GA, Shumak KH, Buskard NA, Blanchette VS, Kelton JG, Nair RC, et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. N Engl J Med 1991;325:393-7.
15	George JN. How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood 2010;116:4060.
16	Page EE, Kremer Hovinga JA, Terrell DR, Vesely SK, George JN. Rituximab reduces risk for relapse in patients with thrombotic thrombocytopenic purpura. Blood 2016;127:3092.