Spinal epidural hematoma (SEH) is a complication of neuraxial anesthesia in the setting of thrombocytopenia and can result in permanent neurologic deficits.1 Severe thrombocytopenia (platelets <50,000 × 109/L)2 is considered a contraindication to neuraxial anesthesia, but due to a paucity of data, there is no defined platelet cutoff value that determines neuraxial safety. There are reports of neuraxial administration in the setting of unknown thrombocytopenia.3 For obstetric indications, neuraxial anesthesia is rarely performed with a platelet count <50,000 × 109/L at our institution, but neuraxial candidacy should be considered on a case-by-case basis. According to the Society for Obstetric Anesthesia and Perinatology (SOAP) recommendations, most obstetric anesthesiologists will place an epidural with a platelet count of 75,000 × 109/L and may consider a lower platelet value in patients with gestational thrombocytopenia or immune thrombotic purpura.4 Neither the American Society of Anesthesiologists (ASA) nor SOAP currently makes an official recommendation of a minimum platelet count for spinal anesthesia, but a risk–benefit discussion and shared decision-making with the thrombocytopenic patient is pertinent. Fortunately, SOAP is currently creating a consensus statement entitled Thrombocytopenia in Pregnancy: Focus on Neuraxial Anesthesia.
We report a parturient who received spinal anesthesia with subsequent discovery of a platelet count of 7000 × 109/L despite a previous normal level earlier in the pregnancy. She was taken to the operating room urgently for cesarean delivery for fetal distress without a preprocedural platelet count. She did not develop signs of an SEH despite severe thrombocytopenia during spinal placement.
The differential for severe thrombocytopenia is broad and warrants early laboratory evaluation for a thrombotic microangiopathy (TMA) such as thrombotic thrombocytopenic purpura (TTP). Given that TTP closely mimics diseases seen frequently in obstetrics, early clinical recognition is difficult. Subtle differences in presentation may lead to suspicion of TTP, but definitive diagnosis depends on laboratory values.
Written Health Insurance Portability and Accountability Act (HIPAA) authorization was obtained from the patient for this case report.
A 24-year-old gravida 2, para 1 at 35 weeks of gestation underwent urgent cesarean delivery for suspected placental abruption in the setting of nonreassuring fetal status. Her history included one uncomplicated vaginal delivery, Mallampati IV airway, and body mass index of 39 kg/m2. The platelet count was pending preoperatively, but was recently 277,000 × 109/L. Preoperative coagulation factors were also unavailable. A concise bleeding history showed no vaginal bleeding and no anticoagulant use. Although placental abruption can be associated with significant coagulopathy, neuraxial anesthesia was chosen over general anesthesia given the nonreassuring airway examination. A spinal anesthetic was administered in one attempt with a Sprotte 24-gauge needle.
Despite confirming abruption, estimated blood loss was only 500 mL. After delivery, the platelet count resulted as 7000 × 109/L. Due to hemostasis and presumed laboratory error, blood was redrawn, and she was transferred to recovery. The repeat platelet count was 11,000 × 109/L. As illustrated in Figure 1, all other coagulation factors were normal (fibrinogen = 337 mg/dL, prothrombin time [PT] = 10.7 seconds, international normalized ratio [INR] = 0.94, activated partial thromboplastin time [aPTT] = 29.3 seconds). Postoperatively, 1 unit of platelets was transfused, hematology was immediately consulted, and frequent examinations showed normal neurologic recovery.
A hemolysis screen (haptoglobin undetectable, lactate dehydrogenase = 4085 U/L, reticulocyte count = 92 × 109/L, hemoglobin = 9.3 g/dL, blood smear with schistocytes) confirmed the diagnosis of a microangiopathic hemolytic anemia (MAHA). A disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13) was deficient (16%), and the ADAMTS13 inhibitor was present, leading to a diagnosis of acquired TTP. The patient developed acute kidney injury and transient confusion several hours after her cesarean delivery. Steroids and plasmapheresis were initiated and continued for 9 days. She was discharged on postoperative day 11 with a platelet count of 190,000 × 109/L (Figure 2). She was readmitted twice for TTP relapse requiring steroids, rituximab, and plasmapheresis, but has since remained stable.
TMAs are MAHAs with thrombocytopenia and end-organ damage and can be inherent in or precipitated by pregnancy.5 TTP is often misdiagnosed as preeclampsia or hemolysis, elevated liver enzymes, low platelet count syndrome (HELLP) because of the overlapping symptoms of hypertension, proteinuria, renal impairment, and liver dysfunction (Table).5,6 TTP differs by persistent severe thrombocytopenia, markedly elevated lactate dehydrogenase, absent coagulopathy, and lack of resolution with delivery.5 In TTP, ADAMTS13, a protease that cleaves von Willebrand Factor (vWF), is usually deficient due to inhibitory autoantibodies (acquired TTP), or rarely from inherent ADAMTS13 gene mutations (congenital TTP).7 The absence of the ADAMTS13 protease leads to platelet aggregation and microthrombus formation, which could explain the low intraoperative blood loss despite severe thrombocytopenia. During pregnancy, increased vWF levels lead to reduced ADAMTS13 protease activity, which can trigger a clinical TTP episode in parturients with underlying congenital TTP.5 Acquired TTP can be provoked by immunologic alterations of pregnancy.5
Differentiating Thrombocytopenia in Pregnancy5,6
||PLEX, rituximab, steroids
||Steroids and/or IVIG if severe
|Resolution with delivery?
|Platelet count (×109/L)
||High suspicion, low ADAMTS13, positive hemolytic screen, markedly elevated LDH
||Elevated liver enzymes, positive hemolytic screen
||Elevated BP, vision changes, RUQ pain, headache, pulmonary edema, proteinuria, liver dysfunction
||Diagnosis of exclusion
||Diagnosis of exclusion, often present before pregnancy
||HTN, proteinuria, renal impairment, liver dysfunction, fever, altered mental status
||HTN, proteinuria, renal impairment, liver dysfunction
||HTN, proteinuria, renal impairment, liver dysfunction
|Common time of onset
||Second trimester and beyond. Most common TMA in first trimester
||Second or third trimester
||First and second trimester
bbreviations: ADAMTS13, a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13; BP, blood pressure; GT, gestational thrombocytopenia; HELLP, hemolysis, elevated liver enzymes, low platelet count; HTN, hypertension; ITP, immune thrombocytopenia; IVIG, intravenous immunoglobulin; LDH, lactate dehydrogenase; PLEX, plasma exchange; Pre-E, preeclampsia; RUQ, right upper quadrant; TMA, thrombotic microangiopathy (microangiopathic hemolytic anemia with thrombocytopenia and end-organ damage; TTP, thrombotic thrombocytopenic purpura.
Viscoelastic testing is available at our institution but was not utilized as the patient was clinically hemostatic with a normal fibrinogen, INR, and aPTT. We focused on determining the cause of the thrombocytopenia. However, viscoelastic testing could have been beneficial to rule out other coagulopathies and may have increased suspicion for TTP. Interestingly, there has been a report of viscoelastic testing in TMAs failing to detect hypercoagulability in vitro, where there is no endothelium to secrete vWF.8
Treatment of acquired TTP consists of plasmapheresis to replete ADAMTS13 and to remove the ADAMTS13 inhibitor from circulation, corticosteroids for immunosuppression, and rituximab for refractory TTP.7,9 In the absence of active bleeding, careful consideration of the differential diagnosis, urgent hematology consultation, and an investigation for MAHA can avoid unnecessary transfusions. Anesthesiologists should be familiar with the pathogenesis and treatment for TTP, as diagnostic delay can increase morbidity and mortality.5,7
Thrombocytopenia in the setting of excellent hemostasis presented a clinical dilemma before diagnosis of TTP. The severity of thrombocytopenia in the postsurgical setting was alarming, but the hemodynamic stability and hemostasis were reassuring. Platelets were initially transfused and deemed an acceptable risk due to concern for postsurgical bleeding, development of SEH, and possible need for further interventions. However, the patient’s risk of SEH development at this point was likely low given the lack of coagulopathy. Risk of SEH increases with epidural catheter placement and removal, and this was fortunately not a consideration because a single-shot spinal was performed.10
Platelet transfusion in TTP is considered to be contraindicated due to case reports of fulminant neurologic aggravation (coma, stroke, seizure, or focal neurologic signs).11 Our patient did not experience any of these symptoms after receiving platelets. Many patients subsequently diagnosed with TTP do inadvertently receive platelets before diagnosis without sequelae. In fact, a 2009 analysis of 382 patients with TTP concluded that there is uncertain evidence for harm from platelet transfusion in TTP.12 There was no difference in mortality or neurologic sequela between patients diagnosed with TTP who received and did not receive platelets.11
Administering neuraxial anesthesia in a healthy parturient without a platelet count is in line with current guidelines published by ASA and SOAP.12 In this case, urgent delivery was necessary, the patient received no anticoagulants, had a previous normal platelet count, and delivered previously without hematologic complications. However, abruption can precipitate coagulopathy, but consideration of the risks of general versus neuraxial anesthesia in this case favored avoiding a general anesthetic. Given her Mallampati IV airway and obesity, general anesthesia posed many risks that neuraxial administration avoided. If the platelet count was known before surgery, neuraxial anesthesia would not have been considered, and debate about how to perform a cesarean delivery with severe thrombocytopenia would have become the dominant consideration.
The risk of SEH formation in TTP is poorly defined but devastating if it occurs, making it important to monitor for signs of neurologic compromise. This patient was assessed every 30 minutes until full return of neurologic function. Prophylactic imaging for SEH formation was considered, but was ultimately deferred unless a neurologic deficit developed. This patient did not develop an SEH, perhaps due to some protective factors. She did not have other risk factors for SEH as she was not coagulopathic and received a single-shot spinal, in one attempt, with a small-gauge pencil-point needle, rather than an epidural catheter.10,13 In addition, TTP induces a paradoxical thrombotic state, and despite having a quantitative platelet deficiency, the quality of the remaining free platelets was intact.14 Therefore, although critically limited in number, the few well-functioning platelets provided hemostasis for surgery and neuraxial anesthesia.
The true correlation between severe thrombocytopenia and SEH formation is unknown because of limited data. There is no registry to document the rare thrombocytopenic patient who receives neuraxial anesthesia, but the development of such a registry would be beneficial and may lead to changes in practice. Increased reporting may demonstrate that the risk of SEH is exceedingly low, even with thrombocytopenia. Each patient must be considered individually; if the risk of general anesthesia is substantial, neuraxial anesthesia, even with severe thrombocytopenia, may be the safest approach. Hematology consultation should be obtained early in patients with severe thrombocytopenia, as prompt recognition and therapeutic intervention are paramount to successful treatment.
Name: Lacey E. Straube, MD.
Contribution: This author wrote and submitted the case report.
Name: Gustaaf G. de Ridder, MD, PhD.
Contribution: This author provided laboratory medicine consultation and edited the case report.
Name: Christopher A. Huber, MD.
Contribution: This author was the anesthesia resident during this case, performed the spinal anesthetic, provided the details of the case, and edited the case report for submission.
Name: Samuel N. Blacker, MD.
Contribution: This author was the attending anesthesiologist during the described case, provided details for the case for submission, researched the implications of thrombotic thrombocytopenic purpura and pregnancy, and edited the case report.
This manuscript was handled by: Markus M. Luedi, MD, MBA.
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