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On-line version ISSN 1806-907X
Rev. Bras. Anestesiol. vol.59 no.2 Campinas Mar./Apr. 2009
Regional anesthesia and non-preeclamptic thrombocytopenia: time to re-think the safe platelet count*
Anestesia regional y trombocitopenia no preclámptica; es hora de pensar de nuevo sobre el nivel seguro de plaquetas
Motoshi TanakaI; Mrinalini BalkiII; Anne McLeodIII; Jose C. A. Carvalho, PhD, FANZCA, FRCPCIV
Anesthesia Fellow, Mount Sinai Hospital, University of Toronto
IIAssistant Professor, Department of Anesthesia, University of Toronto
IIIAssistant Professor, Department of Medicine, University of Toronto
IVAssociate Professor, Department of Anesthesia and Department of Obstetrics and Gynecology, University of Toronto
OBJECTIVES: Although regional anesthesia is widely used for pain control
in obstetrics, it may not be appropriate for patients with thrombocytopenia
due to the risk of neuraxial hematoma. There is no strong evidence to suggest
the minimum platelet count that is necessary to ensure the safe practice of
regional anesthesia. The purpose of this study was to review the safety of regional
anesthesia in non-preeclamptic thrombocytopenic parturients at our institution
over a 5-year period.
METHODS: A retrospective chart review was performed in all the non-preeclamptic obstetric patients who delivered at our facility between April 2001 and March 2006, and had platelet counts < 100 × 109.L-1 on the day of anesthesia. The etiology of the thrombocytopenia, type of anesthesia, mode of delivery and major anesthetic complications were noted.
RESULTS: Seventy-five patients were identified, 47 of whom (62.6%) had received regional anesthesia. The etiology of their thrombocytopenia was immune thrombocytopenic purpura in 49 patients, gestational thrombocytopenia in 20 and other causes in 6 patients. Regional anesthesia was administered in 91.9% of the patients with platelet counts of 80 to 99 × 109.L-1 and in 48.1% of the patients with platelet counts of 50 to 79 × 109.L-1. None of the 11 patients with platelet counts below 50 × 109.L-1 received regional anesthesia. There were no neurological complications.
CONCLUSIONS: In our series, regional anesthesia was safely administered in pregnant patients with platelet counts between 50-79 × 109.L-1. Our results are in keeping with other series in the literature. We suggest that in non-preeclamptic patients with stable platelet counts and no history or clinical signs of bleeding, the lower limit of platelet count for regional anesthesia should be 50 × 109.L-1
Keywords: ANESTHETIC TECHNIQUES: Regional; COMPLEMENTARY EXAMS: platelet count; DISEASES, Hematologic: thrombocytopenia
Y OBJETIVOS: A pesar de que la anestesia regional esté siendo muy
utilizada en el control del dolor en obstetricia, su uso puede no ser muy apropiado
en las pacientes con trombocitopenia, debido al riesgo de hematoma en el neuro
eje. No existen fuertes evidencias que sugieran un número mínimo
de plaquetas necesario para garantizar la seguridad en la realización
de la anestesia regional. El objetivo de este estudio fue analizar la seguridad
de la anestesia regional en pacientes con trombocitopenia no preeclámptica
en la institución durante un período de cinco años.
MÉTODO: Fue realizada revisión retrospectiva de las historias clínicas médicas de todas las pacientes obstétricas no preeclámpticas cuyo parto fue realizado en la institución entre abril de 2001 y marzo de 2006 y que presentaron < 100 x 109.L-1 de plaquetas el día de la anestesia. La etiología de la trombocitopenia, el tipo de anestesia, tipo de parto y las principales complicaciones anestésicas fueron registrados.
RESULTADOS: Se identificaron 75 pacientes, de las cuales 47 (62,2%) recibieron anestesia regional. La etiología de la trombocitopenia incluyó púrpura trombocitopénica inmune en 49 pacientes, trombocitopenia de gestación en 20 pacientes, y otras causas en seis pacientes. La anestesia regional fue utilizada en un 91.9% de las pacientes con nivel de plaquetas entre 80 a 99 x 109.L-1 y en 48.1% de las pacientes con nivel de plaquetas entre 50 y 79 x 109.L-1. Ninguna de las 11 pacientes que presentaban plaquetas por debajo de 50 x 109.L-1 recibió anestesia regional. No hubo complicaciones neurológicas.
CONCLUSIONES: En los casos estudiados, la anestesia regional fue administrada con seguridad en las gestantes con nivel de plaquetas entre 50 - 79 x 109.L-1. En este estudio los resultados son similares a los de otras series relatadas en la literatura. Sugerimos que en las pacientes sin eclampsia y con un nivel estable de plaquetas, y sin historial previo o señales clínicos de sangramiento, el límite inferior de 50 x 109.L-1 debe ser usado.
Thrombocytopenia is a relatively common condition in pregnancy, occurring in up to 10% of patients 1. In non-pregnant patients, the normal platelet count varies between 150 and 400 × 109.L-1. However, several studies have shown that the mean platelet count decreases by approximately 10% in pregnancy, and approximately 1% of pregnant women are found to have a platelet count < 100 × 109.L-1 1-3. Although a variety of obstetric conditions cause thrombocytopenia, most cases are related to gestational thrombocytopenia, immune thrombocytopenic purpura (ITP) or preeclampsia 2. The bleeding risk due to thrombocytopenia varies according to its etiology. Based on the expert opinion by Warkentin et al, unlike preeclamptic patients, destructive thrombocytopenic disorders such as ITP are associated with large, "hyperfunctional" platelets, and consequently there is a possibility of a lower bleeding risk at a given platelet count 4.
Regional anesthesia is currently a standard of practice for labour pain relief in most obstetric units, and all efforts towards its safe use should be encouraged 5. However, the safety of regional anesthesia in the presence of thrombocytopenia has been controversial, due to the risk of neuraxial hematoma and neurological sequelae 6. It is therefore of utmost importance that we continue to investigate the safety of regional anesthesia in this subset of patients.
Cousins and Bromage recommended that epidural punctures should be avoided if the platelet count is below 100 × 109.L-1, based on the studies on bleeding time (BT) 6. This recommendation, however, has been disputed. It has been suggested that it is appropriate to lower the platelet count threshold for insertion of an epidural catheter to 75 to 80 × 109.L-1 in the absence of abnormal coagulation, and that for those with platelet counts of 50 to 75 × 109.L-1, the benefits of regional anesthesia versus the risk of neuraxial hematoma should be weighed 7, 8.
In 2002, the guidelines published by the American College of Obstetricians and Gynecologists suggested that patients with platelet counts between 50 × 109.L-1 and 100 × 109.L-1 might be potential candidates for regional analgesia 9. Although some anesthesiologists will embrace these recommendations and eventually consider regional anesthesia in patients with platelet counts above 50 × 109.L-1, the vast majority will continue to use the cut-off limit of 75 to 80 × 109.L-1.
The origins of this safe lower limit of platelet counts (75 to 80 × 109.L-1) for regional anesthesia are not clear. Very few studies have tried to correlate platelet counts with assays of primary hemostasis. Orlikowski et al. measured platelet counts, thromboelastography (TEG) parameters and BT in healthy pregnant women and in women with preeclampsia/eclampsia 10. They found that the platelet function remained normal until the platelet count decreased to 54 × 109.L-1 (95% confidence limits 40 to 75 × 109.L-1). It is quite possible that the current cut-off limit of 75 to 80 × 109.L-1 came from this particular study, which basically looked at preeclamptic patients. On the other hand, several small patient series have been published supporting the safety of regional anesthesia in patients with platelet counts above 50 × 109.L-1 11-14.
The purpose of this study was to review the use of regional anesthesia in non-preeclamptic thrombocytopenic parturients at our institution, in order to further contribute to data supporting the adoption of a platelet count lower than the current widely accepted 75 to 80 × 109.L-1 as a safe lower limit for regional anesthesia in this specific subset of obstetric patients.
After obtaining approval from the Research Ethics Board, a retrospective chart review was conducted at Mount Sinai Hospital in Toronto. We reviewed the electronic health record data at our facility to identify all women with thrombocytopenia who delivered during the period April 1, 2001 to March 31, 2006. We particularly selected patients with platelet counts below 100 × 109.L-1 on the day of anesthesia and their charts were obtained for detailed reviews. Patients who were diagnosed with preeclampsia or hypertension were excluded. Preeclampsia was defined as sustained systolic blood pressure of at least 140 mmHg or a sustained diastolic blood pressure of at least 90 mmHg after 20 weeks of gestation, and proteinuria in accordance with American College of Obstetricians and Gynecologists guidelines 15. While hypertension was defined as high blood pressure present before 20 week of gestation or present before pregnancy 16.
For each patient, the etiology of the thrombocytopenia (e.g. ITP, gestational thrombocytopenia, etc.), the platelet count on the day of anesthesia, the anesthetic technique (epidural, spinal, general or no anesthesia), the mode of delivery (vaginal or cesarean delivery) and any neurological deficits during hospitalization were identified.
During the study period, 33,692 parturients delivered at our institution, of which 104 (0.3%) had a diagnosis of thrombocytopenia without accompanying preeclampsia or hypertension. Of these 104 patients, 75 had platelet counts × 109.L-1 on the day of anesthesia, and 47 of these 75 patients (62.7%) were administered regional anesthesia for delivery. The etiology of their thrombocytopenia was ITP in 49 patients, gestational thrombocytopenia in 20 patients and other causes in 6 patients (Table I).
The modes of delivery and anesthesia techniques are listed in Table II, according to the categories of platelet count levels on the day of anesthesia. In patients with platelet counts between 80 × 109.L-1 and 99 × 109.L-1 on the day of anesthesia, 34 of the 37 patients (91.9%) received regional anesthesia (17/20 for vaginal delivery, 17/17 for cesarean delivery). In this subgroup, three patients were not administered regional anesthesia for vaginal delivery, but the reasons for not using regional anesthesia were unrelated to their platelet counts. In the subgroup of patients with platelet counts between 50 × 109.L-1 and 79 × 109.L-1 , 13 of the 27 patients (48.1%) received regional anesthesia, while in those with platelet counts less than 50 × 109.L-1 (11 patients), none received regional anesthesia. Out of 28 patients who were not administered regional, 11 had a platelet count of < 50 × 109.L-1; three of which also had bleeding symptoms. The remaining 17/28 patients had a platelet count of > 50 × 109.L-1, and although none of them presented with any bleeding symptoms, regional was denied either by the attending anesthesiologist (n =13) or by the patient herself (n = 4). Among those receiving epidural anesthesia, the lowest platelet count was 63 × 109.L-1, and among those receiving spinal anesthesia, it was 58 × 109.L-1. The incidence of cesarean delivery was 40% (30/75). No serious anesthesia-related complications, such as neurological deficits or paralysis, were identified in this series. Data are presented descriptively only.
Thrombocytopenia constitutes a relative contra-indication to regional anesthesia in obstetrics. The major concern is the risk of neuraxial hematoma secondary to bleeding in patients with decreased platelet levels.
In the general population, the incidence of neuraxial hematoma after epidural and spinal anesthesia has been estimated at 1:150,000, and 1:220,000 respectively 17. In obstetric patients, a recent study of over one million parturients found the incidence of neuraxial hematoma after epidural anesthesia to be 1:168,00018; however, the incidence of neuraxial hematoma after spinal anesthesia is unknown 19.
To our knowledge, only 12 cases of neuraxial hematoma in pregnant patients have been reported in the English language literature, 10 of which have been reviewed by Beilin et al. 20. The first three cases were only diagnosed clinically 19-21, and two of them were found to have narrow lumbar spinal canals on X-ray 21,22, while the etiology in the third case was not mentioned 23. Three other cases were found to be patients with anatomical abnormalities of their spines which were not diagnosed before the initiation of regional anesthesia, two with spinal ependymoma 24,25, and one with neurofibromatosis 26. Two cases had severe preeclampsia with coagulation disorder 27,28. One patient had cholestasis of pregnancy with abnormal coagulation 29. The details in one case were not available 30. The remaining two cases, reported by Moen et al., were identified in a country-wide survey of neurological complications after regional blockade, between 1990 and 1999, in Sweden 31. Both of these patients were severely affected by HELLP syndrome, with apparent signs of coagulopathy. To the best of our knowledge, there are no confirmed case reports of neuraxial hematoma after regional anesthesia in thrombocytopenic parturients who otherwise showed no clinical signs of impaired hemostasis.
As the incidence of neuraxial hematoma after regional anesthesia is very rare, it is difficult to design a prospective and randomized study to determine the lowest platelet count at which anesthesiologists can safely administer regional anesthesia in obstetric patients. Hence it is necessary to rely on the cumulative experience of case and series reports to build a strong body of evidence as to the best clinical practice. Based on our review of the English language literature, six retrospective studies of regional anesthesia in thrombocytopenic parturients were identified (Table III).
Rolbin et al. evaluated the platelet counts of 686 healthy non-pregnant patients of both genders, and 2,204 pregnant women 32. In this study, seven obstetric patients had platelet counts < 100 × 109.L-1, and three of them received epidural anesthesia. One of these three patients had a platelet count between 75 x 109.L-1 and 99 × 109.L-1, and two of them had platelet counts between 50 × 109.L-1 and 74 × 109.L-1. No clinically detectable neurological deficits were observed in this series.
Rasmus et al. reviewed the charts of 2,929 women who delivered in their facility over a period of six months 11. In this study, 24 patients had a platelet counts less than 100 × 109.L-1 during the peripartum period, of which 14 received regional anesthesia including 12 epidurals and two spinals. Among those with platelet counts between 50 × 109.L-1 and 80 × 109.L-1 , five patients received epidurals, while in those with platelet counts less than 50 × 109.L-1 , four patients received regional anesthesia (two epidurals, and two spinals). One patient whose platelet count was 26 × 109.L-1 received spinal anesthesia after a platelet transfusion. There were no neurological complications associated with the anesthesia.
Shaley et al. 12 assessed the safety of epidural anesthesia in 45 women with gestational thrombocytopenia with platelet counts between 50 × 109.L-1 and 100 × 109.L-1. In this study, 33 patients had platelet counts between 75 × 109.L-1 and 100 × 109.L-1, and 12 patients had platelet counts between 50 × 109.L-1 and 75 × 109.L-1. None of the patients developed clinically significant sequelae from the epidural anesthesia during or over a six-day follow-up.
Beilin et al. reported a retrospective chart review of all parturients at their institution who had platelet counts less than 100 × 109.L-1 during the peripartum period from March 1993 to February 1996 33. During this period, 15,919 women delivered in their facility, and 80 women were found to have platelet counts less than 100 × 109.L-1, of which 30 patients had epidural anesthesia (the platelet count range in these patients was between 69 × 109.L-1 and 98 × 109.L-1). They found no documentation of neurological complications in any of these patients.
Webert et al. analyzed the obstetrical management of 119 pregnancies with ITP followed at their institution over an 11-year period 13. In this analysis, epidural anesthesia was performed in 42 parturients. Within this group, 16 women had platelet counts more than 100 × 109.L-1 , 19 women had platelet counts between 76 × 109.L-1 and 100 × 109.L-1 , six women had platelet counts between 50 × 109.L-1 and 75 × 109.L-1 , and one had a platelet count less than 50 × 109.L-1 . No patient had complications related to the placement of an epidural catheter.
A similar review was carried out by Frenk et al., who reviewed the medical records of parturients presenting at their institution with platelet counts < 100 × 109.L-1 between 1997 and 2002 14. One hundred and seventy-seven patients were identified, and 170 of them received regional anesthesia for either vaginal or cesarean delivery. Of the parturients with platelet counts between 60 × 109.L-1 and 100 × 109.L-1, 29 received spinal anesthesia and 131 received epidural anesthesia. In the parturients with platelet counts between 50 × 109.L-1 and 60 × 109.L-1, four received spinal anesthesia and two received epidural anesthesia, while in those with platelet counts less than 50 × 109.L-1, four parturients received regional anesthesia only after receiving platelet transfusions. No neurological complications were documented in any of the patients reviewed.
In addition to these six series, we have identified two case reports of uneventful epidural anesthesia in the presence of significant thrombocytopenia. One of the cases had a platelet count of 4 × 109.L-1, and was diagnosed with Evans' syndrome after delivery 34. The other case was found to have ITP, and her platelet count was 26 × 109.L-1 after the induction of epidural anesthesia 35.
The main reasons for pregnancy-associated thrombocytopenia, defined as a platelet count < 150 × 109.L-1, include gestational thrombocytopenia (74%), hypertensive disorders of pregnancy (preeclampsia) (21%) and ITP (3%) 2. Platelet disorders in gestational thrombocytopenia and ITP are considered static 20, with stable platelet counts and preserved platelet function 4. On the other hand, the disorder in preeclampsia is dynamic. The platelet counts of these patients may fall within a short period of time, and platelet function can be impaired 36-38. Since these two conditions exhibit different patterns with respect to the function of platelets, we excluded the patients with preeclampsia in our study. We believe that preeclamptic patients need different guidelines as to the minimum platelet count for regional anesthesia.
As previously highlighted, the incidence of neurological complications from regional anesthesia as a consequence of thrombocytopenia is extremely rare in obstetric patients. We usually rely on the platelet count to determine if regional anesthesia is feasible or not. Ideally, however, we should be able to evaluate not only the platelet count but also the platelet function, prior to a regional procedure, although this is difficult to do. Platelet aggregometry and flow cytometry are not practical tests because they are time-consuming and require technical expertise 39. The in vivo bleeding time (BT) is no longer regarded as a reliable test for clinical bleeding because it does not necessarily reflect the risk of bleeding at other sites 40, and there is also a wide variation among observers 41. Currently, two bedside instruments are available to evaluate platelet function: the thromboelastogram (TEG) and the platelet function analyser (PFA-100).
Orlikowski et al. 10 studied the platelet count, BT and TEG parameters of normal pregnant patients and 49 patients with preeclampsia, and concluded that the platelet function remained normal until the platelet count decreased to 54 × 109.L-1 (95% confidence limits 40 to 75 × 109.L-1).
Vincelot et al. 42 measured the platelet function in normal pregnancy, in patients with thrombocytopenia of pregnancy and in patients with preeclampsia using the PFA-100 analyser. According to their results, the platelet function in patients with gestational thrombocytopenia may be preserved when the platelet count is as low as 60 × 109.L-1.
Although these studies are important, and constitute further supporting evidence of normal hemostasis in patients with thrombocytopenia, their sample sizes were very small and, hence, no definitive conclusions can be drawn regarding the platelet function of parturients with thrombocytopenia.
Wee et al. recently conducted a nation-wide survey of the practice of neuraxial anesthesia related to coagulation problems in the 264 obstetric units in the UK 43. They found that in parturients with ITP and platelet counts between 80 × 109.L-1 and 100 × 109.L-1, 64 to74% of the units performed regional anesthesia; in those with platelet counts between 50 × 109.L-1 and 79 × 109.L-1, 22 to 31% of the units performed regional anesthesia; and in those with a platelet count below 50 × 109.L-1, 4 to 9% of the units performed epidural anesthesia. This report is very much in keeping with our results, in which most of the parturients with platelet counts more than 80 × 109.L-1 received regional anesthesia, while only 48.1% of those with platelet counts between 50 × 109.L-1 and 79 × 109.L-1 were administered regional.
Based on the combination of these six retrospective studies, two case reports and our own results, a total of 328 patients, with platelet counts between 50 × 109.L-1 and 100 × 109.L-1, who received regional anesthesia without bleeding complications, have been documented. Although each publication stratified patients in a different way, it is clear that at least 40 of those patients had platelet count between 50 and 80 × 109.L-1 (Table III). We believe that there is enough evidence in the literature to support a move towards lowering the safe cut-off value of platelet counts for the practice of regional anesthesia in patients who do not exhibit signs of abnormal bleeding in the presence of non-preeclamptic thrombocytopenia.
In addition, current guidelines published by the British Society for Haematology in 2003 state that asymptomatic ITP patients with platelet counts > 20 × 109.L-1 do not require treatment until delivery is imminent, and platelet counts > 50 × 109.L-1 are regarded as safe for both vaginal delivery and cesarean delivery 44. Similarly, we propose the safe lower threshold of platelet count for the administration of regional anesthesia in non-preeclamptic parturients should be 50 × 109.L-1, since this group of patients is stable without any impairment of platelet function.
Our study was limited by its retrospective nature, as a result of which the anesthetic management was dictated by the attending anesthesiologist, and also the platelet function tests were unavailable in any of these patients prior to their delivery. Future publications of additional series of patients receiving regional anesthesia in the context of thrombocytopenia in pregnancy will help to build up a larger database to solidify our recommendation. In addition, further studies exploring the use of bedside platelet function testing to identify patients with normal coagulation in the presence of thrombocytopenia will help anesthesiologists make better decisions about the safe use of regional anesthesia in this subset of patients.
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Correspondence to: Submitted em 28
de dezembro de 2008 *
Received from Departments of Anesthesia, Obstetrics and Gynecology and Medicine,
Mount Sinai Hospital, University of Toronto, Ontario, Canada
Dr. Jose C. A. Carvalho, MD
Department of Anesthesia and Pain Management, Mount Sinai Hospital
600 University Avenue, Room 781
Toronto, Ontario, M5G 1X5, Canada
Accepted para publicação em 05 de janeiro de 2009
Submitted em 28
de dezembro de 2008
* Received from Departments of Anesthesia, Obstetrics and Gynecology and Medicine, Mount Sinai Hospital, University of Toronto, Ontario, Canada