Gaucher disease (GD) is a common inborn error of metabolism resulting in accumulation of glycolipids in lysosomes due to a deficiency in β-glucocerebrosidase.1 The prevalent phenotype (type 1) occurs in approximately 1 in 75,000 births and is characterized by a preponderance of lipid-filled macrophages within multiple tissues including bone marrow, spleen, and liver. This results in the development of a chronic inflammatory environment with varied pathophysiological findings. Thrombocytopenia and defects in coagulation in GD are common and have been ascribed to impaired hematopoietic function, splenic sequestration, and altered production of coagulation factors. The mainstay of treatment is enzyme replacement therapy with adjunctive substrate reduction, splenectomy, and/or bone marrow transplant.
Thrombocytopenia (platelet count <150,000/mm3) is a common finding in pregnancy, occurring in up to 10% of parturients. Guidelines for placement of labor epidural in patients with thrombocytopenia are mainly derived from broad retrospective studies or small case series.2,3 Due to the relative rarity of epidural or spinal hematomas, there is a need for studies with large sample size to properly power for prospective trials examining this complication.4 Historically, a platelet count of 100,000/mm3 has been recommended as the lower limit of safety for neuraxial anesthesia. However, clinical practice among anesthesiologists varies widely and a small number of retrospective case series have documented epidural placement in parturients with platelet counts as low as 56,000/mm3 without complications.2,5,6 This is not without controversy and has scant supporting data beyond retrospective case series. We used thromboelastography (TEG) to assist in the determination of the safety of placing an epidural catheter and to plan for potential peripartum bleeding.
Written informed consent for publication was obtained from the patient.
A 31-year-old woman G4P1 (G4P1021) with a history of type 1 GD treated by enzyme replacement (imiglucerase 4000 units every 2 weeks) during pregnancy presented at 37 weeks plus 1 day for induction of labor in the setting of gestational hypertension (GHTN) and thrombocytopenia. The patient had originally been diagnosed with GD 9 years before presentation after delivery of her first child. At that time (before enzyme replacement), she had postpartum hemorrhage associated with pancytopenia and thrombocytopenia. Her platelet levels had a nadir of ~80,000/mm3 and white blood cells of 1.3/mm3. The volume of hemorrhage was not available for the prior event 9 years ago, but she did not require transfusion. Bone marrow biopsy confirmed the diagnosis of GD, and her hematologist further diagnosed her with Gaucher hypersplenism. Since initiation of enzyme replacement, after her postpartum hemorrhage, she did not have any clinical signs of bleeding.
Her current presentation was concerning for preeclampsia with severe features versus GHTN with thrombocytopenia secondary to GD. Table 1 shows the patient’s platelet counts and blood pressures (BPs) during different admissions. At 30 weeks plus 2 days with BP of 140/86 and 145/93 mm Hg, platelet count of 127,000 mm3, without proteinuria and normal laboratory findings for preeclampsia, she was diagnosed with GHTN. Two days before elective induction of labor, her platelet count was 56,000/mm3, prothrombin time (PT) 10.5 seconds, international normalized ratio (INR) 0.9, and partial thromboplastin time (PTT) 30 seconds. All other laboratory values were within normal limits (lactate dehydrogenase 566 U/L, fibrinogen 371 mg/dL, spot urine protein/creatinine ratio 0.2, uric acid 4.6 mg/dL, aspartate aminotransferase 20 U/L, and alanine aminotransferase 23 U/L). On presentation for induction of labor (37 weeks plus 1 day), she had BPs ranging from 141/92 to 154/88 mm Hg with platelets of 59,000 mm3. At that time, her diagnosis was either preeclampsia with severe feature versus GHTN with a GD flare.
After induction of labor, the patient requested an epidural catheter for labor analgesia. Her platelet counts from the prior 3 days ranged between 56,000 and 73,000/mm3 without a clear trend toward increase or decrease, with a differential diagnosis of GD flare, hypersplenism, preeclampsia, gestational thrombocytopenia, occult hemorrhage, atypical thrombocytopenic thrombotic purpura, HELPP syndrome (hemolysis, elevated liver enzymes, and low platelet counts), autoimmune thrombocytopenia, drug reaction, and/or infection. The patient interview was conducted shortly after her arrival, before induction, in which the patient denied any signs of coagulopathy such as prolonged bleeding, easy bruising, gingival bleeding, etc. On physical examination, the patient did not have any signs of bleeding around her intravenous site, mouth and gums, or evidence of petechial rash. During the consent process, we discussed the use of parenteral opioids and platelet transfusion with subsequent epidural placement as possibilities. Opioid analgesics were undesirable by both the patient and her obstetrical team due to the risk of respiratory compromise in the newborn, and the patient vehemently denied systemic opioids. Platelet transfusion would have exposed the patient to the risks of transfusion such as alloimmunization or allergic reactions, which was unacceptable to the patient. The discussion with the patient and her family involved both the anesthesiology and obstetric teams, and strong emphasis was placed on the increased risk of complications from epidural analgesia without the ability to predict percent increased risk due to minimal evidence about patients with similar presentation; specifically, the increased risk of epidural hematoma, need for surgical intervention due to epidural hematoma and paralysis was discussed with the patient with emphasis on increased risk. Because her history and physical examination did not reveal any evidence of increased risk of bleeding, we chose to perform TEG to assess for coagulopathy and platelet function in light of normal coagulation studies with PT, PTT, and INR.
Her TEG results are shown in the Figure. Despite thrombocytopenia, her coagulation and clot formation parameters were within normal limits (Table 2). The clot formation times and fibrinolysis were similar to those in the cited studies, while the α-angle and maximum amplitude were lower than those observed for a normal term parturient. We interpreted these values to indicate rapid clot formation without fibrinolysis but a slightly weaker clot than expected for pregnancy. However, the clot strength was still within normal range. These results were in accordance with lack of coagulopathy by history and physical examination, so a lumbar epidural catheter was placed for labor analgesia without complications by an experienced anesthesiologist. After successful uncomplicated vaginal delivery, the platelet count was rechecked and found to be 63,000/mm3, and epidural catheter was removed without complications followed by serial neurologic examinations. On postpartum day 1, patient had no neurological abnormality, epidural site was without tenderness or ecchymosis, and platelet count was 79,000/mm3. She was subsequently discharged without complications.
TEG is a dynamic integrated assay of coagulation, clot formation and strength, as well as fibrinolysis in whole blood. This assay has found utility in situations where standard coagulation assays and complete blood counts may take too long to perform or do not provide enough information about the entire hemostatic cascade. Faster and stronger clot formation consistent with the known hypercoagulability of pregnancy has been demonstrated using viscoelastic assays and decreased fibrinolysis.7–9
Patients with GD are at higher postpartum bleeding risk, and TEG has been suggested for following coagulopathy in perioperative settings.10,11 Additionally, enzyme replacement during pregnancy in patients with GD has been shown to potentially reduce bleeding complications.12 Here, we detail the use of TEG to assist in evaluation of the complex hemostatic milieu of a parturient with GD requesting neuraxial analgesia for labor. While no definitive clinical trials exist to guide anesthesiologists in cases of peripartum thrombocytopenia, multiple retrospective case series suggest that neuraxial anesthesia may be safe with platelet counts as low as 75,000/mm3.2,3,6 No clinical data exist to guide clinical decisions for neuraxial anesthesia in parturients with GD. Our patient had multiple possible etiologies resulting in thrombocytopenia, and use of TEG for this patient allowed rapid evaluation of her hemostatic status. This provided useful information for the choice to place a labor epidural catheter and plan for potential bleeding risks surrounding vaginal delivery or cesarean delivery; more specifically, because the patient had no evidence of increased bleeding on history, physical examination, and standard coagulation panels (PT, PTT, INR), we elected to perform TEG. Had TEG revealed any evidence of increased risk of bleeding, we would have concluded that the risk of bleeding would outweigh the benefit of epidural analgesia.
Both the anesthesiology and obstetric teams’ goal was to deliver the best peripartum experience for the patient. An abnormal TEG result would point to a higher risk of bleeding complication in this setting, but a normal TEG with no evidence of coagulopathy from history, physical examination, and standard coagulation studies supported the decision to offer neuraxial analgesia. This approach may be useful for evaluation of hemostasis and safety of neuraxial anesthesia in patients with marginal platelet counts or potential coagulation defects.
The authors thank Lydia Grondin, MD, Associate Professor of Anesthesiology, University of Vermont Larner College of Medicine, Burlington, VT; and Ralph Yarnell, MD, Assistant Professor of Anesthesiology, University of Vermont Larner College of Medicine, Burlington, VT.
Name: William G. Tharp, MD, PhD.
Contribution: This author helped with patient enrollment and follow-up, data collection and analysis, writing and editing the article drafts.
Name: Borzoo Farhang, DO, MS.
Contribution: This author helped with study invention and design, data analysis and draft edits.
This manuscript was handled by: Raymond C. Roy, MD.
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