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Anaesthesia, 2004, 59, pages 255–264 .....................................................................................................................................................................................................................


Thrombocytopenia in the parturient
P. C. A. Kam,1 S. A. Thompson2 and A. C. S. Liew3
1 Professor of Anaesthesia, Department of Anaesthesia, University of NSW at St. George Hospital, 2 Fellow in Anaesthesia, Department of Anaesthesia, St. George Hospital, 3 Staff Specialist Anaesthetist, Department of Anaesthesia, University of NSW at St. George Hospital, Belgrave Street, Kogarah, NSW 2217, Australia Summary

Thrombocytopenia in pregnant women can be associated with substantial maternal and neonatal morbidity. It may result from a range of conditions and early implementation of some specific treatment may improve both maternal and neonatal outcome. In this review we discuss the clinical features of the more common causes of thrombocytopenia associated with pregnancy, and provide an overview of the anaesthetic considerations.

Pregnancy. Thrombocytopenia; gestational thrombocytopenia, pre-eclampsia, HELLP, thrombotic thrombocytopenic purpura, immune thrombocytopenic purpura.

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Correspondence to: Dr P. C. A. Kam E-mail: Accepted: 26 October 2003

Thrombocytopenia occurs in approximately 10% of pregnant women and may be caused by a variety of obstetric conditions (Table 1) [1]. Although some of these diseases are not associated with adverse effects or outcomes of pregnancy, others can be associated with serious maternal as well as fetal ⁄ neonatal morbidity and mortality. A multidisciplinary team approach involving obstetrician, haematologists, paediatricians and anaesthetists is essential for the optimal management of pregnant women with thrombocytopenia. Thrombocytopenia in the obstetric patient may be the result of a range of conditions, from benign disorders such as incidental gestational thrombocytopenia to life-threatening syndromes such as the ‘haemolysis, elevated liver enzymes, low platelets’ syndrome (HELLP) [2]. The diagnosis of specific disorders is often difficult because the time of onset of these disorders during pregnancy and their clinical manifestations often overlap. The aim of this article is to review the differential diagnosis of thrombocytopenia in pregnancy and highlight the clinical features and management of the various diseases that cause thrombocytopenia, and to summarise the anaesthetic considerations in the management of thrombocytopenia in the parturient.
Ó 2004 Blackwell Publishing Ltd


Sources for this review include Medline 1980–2003 searched under the following Medical Subject Headings: thrombocytopenia, pregnancy, platelets, pre-eclampsia, HELLP, and thrombotic thrombocytopenic purpura (TTP). The bibliographies of the included studies were scanned for additional references (reference dredging). The National Library of Medicine Pub Medical internet site was also used.
Haemostatic changes in normal pregnancy

During normal pregnancy, major changes in haemostasis include increasing concentrations of most clotting factors, decreasing concentrations of some natural anticoagulants and diminishing fibrinolytic activity [3]. These changes create a state of hypercoagulability that is most marked around term and the immediate postpartum period, thereby decreasing bleeding complications that may be associated with delivery. The most important initial factors for haemostasis at delivery, however, are uterine muscle contractions and constriction of the spiral arteries that interrupt blood flow.

...... Platelet activation......l)1 as severe thrombocytopenia.. In pregnancy.. Thrombocytopenia is caused either by increased platelet destruction or decreased platelet production. C. quinine) Systemic lupus erythematosus Antiphospholipid syndrome Disseminated intravascular coagulation Amniotic embolism Disorders with reduced platelet production Congenital thrombocytopenia Aplastic anaemia Leukaemia Drug-induced Myelodysplasia All blood coagulation factors except XI and XIII increase during normal pregnancy [4. occur in parallel in the first half of pregnancy...... The quantitative decrease in platelet count is balanced by enhanced platelet reactivity [17]. the clotting mechanism is activated and factor VIII activity transiently increases after delivery.. . suggesting that a compensated state of progressive platelet destruction occurs during the third trimester [9.. occurs in 5–8% of all pregnant women and accounts for 75% of pregnancy-associated thrombocytopenia..... Thrombocytopenia in the parturient Anaesthesia... The concentration of plasma b-thromboglobulin (a specific protein in the a-granules that is secreted during platelet activation) increases in the second and third trimesters of pregnancy [11].. A. 13]... but then diverge because of a two-fold increase in von Willebrand factor antigen... The normal platelet count range in non-pregnant women is 150–400 · 109.. Antithrombin and protein C levels are normal during pregnancy... or platelet consumption [15]...... the plasma concentration of free protein S decreases markedly during pregnancy and may contribute to the hypercoagulable state [6....l)1 in late pregnancy and labour. malaria) Drug-induced (heparin.P. Æ Table 1 Causes of thrombocytopenia in pregnancy. Significant increases in fibrinogen degradation products occur in 21% of parturients during labour.....l)1......... and fibrinolytic activity decreases rapidly [7]... Kam et al...... The increase in factors VII and X is highest in midpregnancy and remains high in the third trimester... and increased trapping or destruction at the placenta [16]... Gestational or incidental thrombocytopenia Gestational or incidental thrombocytopenia. The decreased platelet count may be related to haemodilution and ⁄ or accelerated platelet turnover with increased platelet production in the bone marrow. In uncomplicated pregnancies.. The features of gestational thrombocytopenia include a platelet count usually below 70 · 109. In the pregnant women.. and returns to normal within 1 h after placental delivery.. with 32% showing the similar increases in the immediate postpartum period. Incidental thrombocytopenia in pregnancy is usually 256 benign.. penicillin... Normal Incidental or gestational thrombocytopenia Pseudothrombocytopenia (laboratory artefact with EDTA anticoagulant) Disorders with increased platelet consumption Immune thrombocytopenic purpura Pregnancy induced hypertension ⁄ HELLP syndrome Thrombotic thrombocytopenic purpura Haemolytic uraemic syndrome Infection-associated (HIV..... the most common cause of thrombocytopenia during pregnancy.l)1 are defined as mild thrombocytopenia.. pages 255–264 .... have described decreased platelet activation mediated by a plasma factor that selectively inhibits prostaglandindependent activation during pregnancy [18].... However...l)1 which returns to Ó 2004 Blackwell Publishing Ltd . elevated liver enzymes. thrombocytopenia is defined as a platelet count of less than 150 · 109.. shortening coagulation times [14]......5–4 g.... 2004...... abnormal platelet activation...... coagulation and fibrinolytic activity are enhanced during delivery [7]. The increase in the concentration of the two components of the factor VIII complex. The plasma fibrinogen concentration increases from non-pregnant levels of 2.. 59......... fibrinogen degradation remains elevated in only 10% of women....... low platelet (HELLP) syndrome....l)1.. The level of tissue factor pathway inhibitor increases in pregnancy...... recent studies have reported that the platelet count decreases by an average of 10% during the third trimester as a result of haemodilution or accelerated destruction leading to younger and larger platelets [8]....... haemolytic uraemic syndrome.. 10]. however...... and pre-eclampsia... At 24–72 h after delivery. 5]... The mean platelet volume increases.. Factor VIII and von Willebrand factor (VWF) antigen..... Increased destruction or utilisation of platelets during pregnancy occurs in microangiopathies (exposure to abnormal blood vessels) such as thrombotic thrombocytopenic purpura.. counts of 100–150 · 109... counts of 50–100 · 109......... increased platelet destruction may be mediated by immunological mechanisms. sulphonamides.l)1 to 6 g...... Platelet count returns to normal 24–72 h postpartum [12... Factor XIII concentrations fall to about 50% of the normal non-pregnant value at term. Some authors.... Plasma fibrinolytic activity is reduced during pregnancy and labour.... The diminished fibrinolysis is caused by increased concentrations of plasminogen activator-1 derived from endothelial cells and plasminogen activator inhibitor-2 derived from the placenta... Factor XI concentrations decrease to approximately 60% of the non-pregnant values...l)1 as moderate thrombocytopenia........... and counts of less than 50 · 109.. During placental separation..... Most blood coagulation inhibitors are unchanged. 7]............... haemolysis..... rifampicin...

.6% of women with idiopathic thrombocytopenia (p = 0..... It appears that there are no specific diagnostic tests that can distinguish gestational thrombocytopenia from mild idiopathic thrombocytopenia....... Pregnancy does not alter the clinical course of ITP... underlying autoimmune disease or a platelet count <50 · 109...... Women with gestational thrombocytopenia are not at a risk of either maternal haemorrhage or fetal haemorrhage. to document a normal neonatal platelet count and a restoration of a normal maternal platelet count after delivery... symptoms or laboratory tests....... However.l)1 [9........ In contrast...... The patient produces IgG antiplatelet antibodies that recognise platelet membrane glycoproteins.... antiplatelet antibodies are present in only 80% of cases.l)1... A... Therefore........ If a thrombocytopenic but otherwise healthy pregnant woman has a platelet count >70 · 109. The antibody-coated platelets are then destroyed by the reticuloendothelial system (primarily the spleen) at a rate that exceeds the capacity of the bone marrow to produce new platelets... pages 255–264 P... The women are asymptomatic with no history of bleeding and thrombocytopenia is usually detected as part of antenatal screening.l)1 and no bleeding do not usually require immediate treatment. absence of splenomegaly..... to detect levels that decrease below the 50–70 · 109. and gingival bleeding preceding pregnancy. Patients with platelet counts >30 · 109........... 59... Antiplatelet antibody tests do not differentiate gestational thrombocytopenia from idiopathic thrombocytopenia.24).. Kam et al. In patients with mildly decreased platelet count and with no prior history of thrombocytopenia......3% women with gestational thrombocytopenia (p < 0.. However. In a study of 250 pregnant women with thrombocytopenia (90 with idiopathic thrombocytopenia. A history of prior thrombocytopenia...l)1) with or without peripheral megathrombocytes.............. It is the most common cause of significant thrombocytopenia in the first trimester......... ITP is a diagnosis of exclusion because there are no pathognomonic signs... petechiae.. because platelet-associated IgG may be elevated in both diseases [21].. Further investigations must be undertaken in pregnant women who are symptomatic or who do not regain a normal postpartum platelet count.l)1 in the first trimester that declines progressively as the pregnancy progresses is consistent with ITP.. a pathological cause of thrombocytopenia becomes substantially more likely........9% of women with idiopathic thrombocytopenia had indirect IgG compared with 60.. An immunological test that measures antibodies that react with specific platelet glycoproteins (monoclonal antibody immobilisation of platelets) cannot differentiate these two syndromes consistently [23]. Symptoms of haemorrhage are rare unless the platelet count is <20 · 109. However..... Æ a normal level following delivery within 12 weeks.l)1. ITP is an insidious disease with initial symptoms such as easy bruising and petechiae.5% of women with gestational thrombocytopenia and in 64.l)1 makes the diagnosis of ITP more likely...Anaesthesia. Immune thrombocytopenic purpura (ITP) ITP is characterised by immunologically mediated platelet destruction and an increase in circulating megathromboÓ 2004 Blackwell Publishing Ltd cytes.. 23].... a meticulous physical examination... 160 with presumed gestational thrombocytopenia) that evaluated eight different platelet antibodies.. platelet-associated IgG was elevated in 69............l)1 and no history of previous thrombocytopenia.. Gestational thrombocytopenia is a diagnosis of exclusion. normal or increased number of megakaryocytes detected by bone marrow aspiration..... the only means of differentiation is to monitor platelet counts closely. investigations are only required when thrombocytopenia occurs early in pregnancy or progressively decreases during the pregnancy or when the platelet count is less than 70 · 109..... when a platelet count is below 70 · 109.. Although 85.l)1. 2004.. Platelet transfusion is indicated if bleeding occurs or if the platelet count is <30 · 109. epistaxis.... The women have no history of thrombocytopenia prior to pregnancy but may have thrombocytopenia in previous pregnancies..... mild thrombocytopenia occurring in the second or third trimester and not associated with proteinuria or hypertension indicates incidental or gestational thrombocytopenia [24]. C.... ITP occurs in approximately one case of thrombocytopenia per 1000 pregnancies and accounts for 5% of cases of pregnancy-associated thrombocytopenia [22]..... Most women with ITP have a history of bruising easily...... there are anecdotal reports of deterioration of symptoms during pregnancy and improvement postpartum [2]....... and exclusion of systemic diseases or drugs that are known to cause thrombocytopenia... in the absence of a platelet count prior to pregnancy. .. From a clinical view. it can be difficult to distinguish ITP from gestational thrombocytopenia...... The four consistent features that are associated with the condition are persistent thrombocytopenia (platelet count <100 · 109... although some may be asymptomatic.. In non-hypertensive pregnant women. There is an extremely low risk of fetal or neonatal thrombocytopenia [19]... Gestational thrombocytopenia usually occurs in the late second or third trimester.. careful blood pressure assessment and monitoring and a peripheral blood film examination should be undertaken.. significant overlap existed and limited its clinical value [21]. The confirmation of normal platelet count prior to pregnancy decreases the probability of an underlying immune thrombocytopenic purpura [20]..........001)............ Thrombocytopenia in the parturient .. More aggressive measures may be required to increase the platelet count to 257 .l)1 range. a platelet count <100 · 109.

.. The major fetal risk is intracranial haemorrhage causing neurological sequelae or death..... the responses are often transient and multiple courses of treatment may be required. and delivery by Caesarean section undertaken if the fetal platelet count is <50 · 109....... The most reliable predictor of fetal thrombocytopenia is the presence of thrombocytopenia at delivery of a prior sibling [29]...... Clearance of Ó 2004 Blackwell Publishing Ltd . Abnormal expression of cell adhesion molecules...... The maternal consequence of ITP is haemorrhage..l)1 [34]. Bleeding complications are usually associated with surgical incisions (such as episiotomy) and lacerations of the birth canal. this approach has not been subjected to randomised controlled studies and has been recently been questioned [ Umbilical cord platelet counts should be measured from umbilical blood obtained at delivery regardless of the method of delivery..l)1. Æ a level to allow epidural analgesia for labour and adequate haemostasis during These changes lead to platelet activation..... Kam et al.... Thrombocytopenia in the parturient Anaesthesia........ generalised endothelial dysfunction and hypertension [39].P....... 59.... this finding is not specific and does not provide an immunological basis for the thrombocytopenia [40]. High doses of intravenous immunoglobulin (2 mg. 32].. and occurs in 6% of all pregnancies [35].. although the latter is associated with bleeding and fetal bradycardia ( 1%) [30]. with reduction of doses until the platelet count stabilises at 75–100 · 109.. The mother is not at a greater risk of abruptio placentae or placenta praevia than the general pregnant population [26]..... pages 255–264 have been recommended for pregnancy-associated ITP [24].. Circulating platelets adhere to damaged or activated endothelium.......... pregnancy-induced hypertension and premature rupture of placental membranes........ They are not at higher risk for postpartum uterine bleeding because myometrial contractions produce mechanical haemostasis without a significant contribution from platelets. although some authors recommend a platelet count >100 · 109...... Cook and colleagues reviewed literature that included 474 pregnant women with ITP and reported that the incidence of intracranial haemorrhage among neonates with severe thrombocytopenia (<50 · 109.. 2004..l)1 is usually adequate in this regard.. and vascular endothelial cell growth factor and its receptor by trophoblasts in pre-eclampsia have been reported [37... In 1977.... ....... The neonate of a mother with ITP may develop ITP as a result of the transplacental transfer of maternal antiplatelet IgG [24]..l)1 [25]..l)1 for delivery................... Although increased levels of platelet-associated IgG are detected in patients with pregnancy-induced hypertension (PIH). steroid therapy increases the incidence of gestational diabetes. Splenectomy may be required during pregnancy to decrease platelet destruction in patients who are refractory to steroid or IgG therapy......... C. prostaglandins and endothelin by placental tissues.. The pathological lesions of pre-eclampsia involve deficient remodelling of the maternal uterine vasculature by the placental trophoblast early in pregnancy [36]. A literature review of 18 studies on maternal ITP that involved 601 neonates showed that 12% of neonates had severe thrombocytopenia........ a case report of intracranial haemorrhage after a vaginal delivery of a thrombocytopenic infant to a mother with ITP led to the recommendation that women with ITP should be delivered by Caesarean section.... Patients with low platelet counts should receive steroids at around 37 weeks of gestation in order to increase maternal and foetal platelet counts.. This causes uteroplacental vascular insufficiency leading to abnormal release and metabolism of nitric oxide..... Drug therapy usually commences with oral prednisone (1–2 mg...... However..... causing enhanced platelet clearance. platelet counts may be <20 · 109..... Betamethasone or dexamethasone is preferred because placental enzymes inactivate a major portion of the prednisone dose that is presented to the placental circulation...24 h)1) developing after 20 weeks of gestation.. The neonate’s platelet count is usually normal by 1 month of age... Daily monitoring of platelet numbers in the neonate is necessary because neonatal platelet count can decrease for 4–5 days post delivery....l)1 [27]......... At delivery... Pre-eclampsia and HELLP syndrome Pre-eclampsia is characterised by hypertension and proteinuria (> 300 mg....... 10–20% of these neonates have platelet counts below 50 · 109....... 38].. A..... but this is rare [28]...... However.. A platelet count >50 · 109.l)1) was 4% after Caesarean delivery and 5% after vaginal delivery [31]. However..... It should be performed in the second trimester because surgery can cause premature labour in the first trimester and may be more difficult in the third trimester due to the large gravid uterus.. Platelet counts below 20 · 109.. in 5%..l)1 should be augmented using platelet transfusions.. There is no consistent and reliable correlation between the fetal platelet numbers at delivery and the severity of maternal thrombocytopenia or the concentration of maternal antiplatelet IgG [21. It is currently recommended that fetal platelet count using percutaneous umbilical blood samples should be measured first. but that intracranial haemorrhage only occurred in 1% (6 ⁄ 601) of neonates and was not related to the mode of delivery [33]. 27]. Determination of fetal platelet count can only be achieved by fetal scalp sampling during labour or percutaneous umbilical 258 blood sampling.... Platelet numbers should be maintained above 50 · 109..l)1 and.

... If pre-eclamptic patients deteriorate or remain thrombocytopenic after delivery. Caesarean section is required in 60% of cases [42].. Approximately 60% of babies die in utero. central neurological abnormalities. Pre-eclampsia is present in 21% of cases of maternal thrombocytopenia [28].... plasma exchange and ⁄ or corticosteroids should be considered to reverse the abnormalities [6.. ADAMTS 13.... and especially those with intrauterine growth retardation [15].. The HELLP (haemolysis.. increased platelet volume and increased megakaryocyte production have been observed [2].. occurs in a slightly younger age group (19 years vs 25 years).......... C... Accelerated platelet destruction. Platelet function may also be impaired in women with pre-eclampsia even if their platelet count is normal... The perinatal mortality is about 22% and is caused by placental abruption.. It has been suggested that the underlying primary pathological lesion in the HELLP syndrome might be endothelial dysfunction and Ó 2004 Blackwell Publishing Ltd damage. thrombocytopenia. a variant of pre-eclampsia. fever and renal dysfunction. Early delivery of the fetus is warranted if there are threats to fetal or maternal life or if the syndrome develops beyond 34 weeks of gestation.. which leads to platelet aggregation. Thrombotic thrombocytopenic purpura (TTP) and haemolytic uraemic syndrome (HUS) Thrombotic thrombocytopenic purpura is characterised by microangiopathic haemolytic anaemia. A deficiency of a VWF-cleaving protease...... Æ IgG-coated platelets may be further increased by the reticulo-endothelial system and platelet activation due to thrombin generation [2].... In some series.. acute renal failure.. pages 255–264 P... The thrombocytopenia is usually moderate and clinical haemorrhage is uncommon unless the patient develops disseminated intravascular coagulopathy. has been identified as a causative factor in the pathogenesis of TTP [48]. Microthrombi deposited in the liver sinusoids cause obstruction to hepatic blood flow.. prothrombin time and fibrinogen concentrations are normal...... 2004.. Although platelet activation has been suggested in the pathogenesis of preeclampsia or HELLP syndrome. However.... low platelets) syndrome. Only neonates born prematurely are at risk of neonatal thrombocytopenia...... A decreasing maternal platelet count is considered as an early sign of worsening of preeclampsia and may occur even before other clinical manifestations of the disease are apparent.l)1 and does not cause fetal bleeding complications [28]..... consumption and eventually thrombocytopenia. which need not be associated by proteinuria and hypertension... The HELLP syndrome is associated with disseminated intravascular coagulation. Platelet transfusions increase the platelet count prior to Caesarean section....... ... SGOT > 70 units. 59. Thrombocytopenia in the parturient . the lifespan of the transfused platelets is shortened..... 43].. impaired prostacyclin production and increased deposition of fibrin within the vascular bed have been suggested. Activation of the coagulation cascade occurs in most preeclamptic patients....... platelet activation.....Anaesthesia..... TTP usually occurs in the second trimester... A....l)1) and is associated with a maternal mortality of about 3... but routine tests such as activated partial thromoboplastin time.. The pathogenesis of thrombocytopenia in women with severe preeclampsia is unknown.......... 45].... are common symptoms.. and thrombocytopenia (<100 · 109. consequently leading to liver distension and elevations of liver enzymes [42].... The management of pre-eclampsia and HELLP is focussed on stabilising the mother until fetal maturity is more favourable........ An increased response of platelet calcium to arginine vasopressin preceding thrombocytopenia as early as in the first trimester has been reported and has been proposed as a possible predictor of the development of the disease [41].......l)1.... Thrombocytopenia occurs in 50% of pre-eclamptic patients and occasionally precedes other manifestations of the disease..... placental abruption...... elevated liver enzymes..... However........ Kam et al..3%.. The clinical manifestations of haemolytic uremic syndrome are similar to that of TTP except that renal 259 .. up to 10% of all cases of TTP occurred in pregnant patients. Term infants of mothers with PIH are no more likely to be thrombocytopenic than those of normal mothers... Thirty percent of the infants (average gestational age 32 weeks) are small for gestational age.......... intrauterine asphyxia... prophylactic treatment of high-risk pregnant women with low-dose aspirin does not significantly decrease the incidence of pre-eclampsia [44].... and prematurity... although vascular endothelial damage. is characterised by microangiopathic anaemia. adult respiratory distress syndrome and intrauterine death. and thrombocytopenia is present in 25% of these... Severe epigastric or right upper quadrant abdominal pain.......... and pregnancy is considered to be a predisposing factor for this disease [47]. fibrinogen D-dimers and thrombin-antithrombin complexes are elevated in most cases......... Fetal monitoring is mandatory.. This deficiency may be caused by mutations in ADAMTS 13 gene in the congenital variant [49] or may result from antibodies against the protease in the acquired form of the disease. and can manifest in approximately 30% of cases postpartum [42. with a mean onset of 23 weeks [50]. It is more common in multiparae... Coagulopathy associated with PIH-related disseminated intravascular coagulation should be treated with fresh frozen plasma or cryoprecipitate if fibrinogen levels are low............ and will help to decide whether early delivery of the fetus is warranted.. The platelet count in neonatal thrombocytopenia associated with pre-eclampsia is rarely below 20 · 109........

. especially in the presence of Ro. dyspnoea. AFLP is most common in primiparae and affects one of 5000–10 000 pregnancies........ Maternal autoantibodies can cross the placenta and cause fetal thrombocytopenia.. Circulating platelet numbers and their function determine the safety of regional anaesthesia....... HUS.... As in the HELLP syndrome. Anaesthetic considerations Mild microangiopathic haemolysis and thrombocytopenia are observed in acute fatty liver of pregnancy (AFLP) [50]..... dysfunction is more severe in HUS whereas neurological abnormalities are more pronounced in TTP.. The choice of anaesthetic technique in the pregnant women with thrombocytopenia largely depends on the proposed method of delivery...2–3....... amniotic fluid embolism.. schistocytes... Drug-induced thrombocytopenia occurs in pregnant as well as non-pregnant women.7 in 100 000 obstetric epidural blocks [59].l)1..... TTP = thrombotic thrombocytopenic purpura. In 75% of these patients..... However plasma exchange is less effective in reversal of renal dysfunction for pregnancy-associated HUS.. Quinidine and sulphonamides are among the most common drugs associated with acute thrombocytopenia [54]... Two 260 Ó 2004 Blackwell Publishing Ltd ... 2004......... HUS = haemolytic uraemic syndrome. A... Acute fatty liver of pregnancy Disseminated intravascular coagulation can be associated with obstetric disorders such as placental abruption.. uterine rupture and intrauterine fetal death and may cause thrombocytopenia. In systemic lupus erythematosus (SLE) about 14–25% of patients develop thrombocytopenia caused by antiplatelet autoantibodies or circulating immune complexes [51]..... although there are no supporting data [60].. Approximately 28–42% of SLE patients have antiphospholipid and ⁄ or lupus anticoagulant. Thrombocytopenia in the parturient Anaesthesia........ Pregnant women suffering from antiphospholipid syndrome may have thrombocytopenia secondary to thrombosis. Æ Table 2 Clinical and laboratory features of HELLP. which is caused by the enhanced clearance of platelets that bind to abnormal von Willebrand Factor molecule. history of recent or current bleeding and other significant medical history. Management of patients with AFLP is supportive with emphasis of correction of hypoglycaemia.... Feature Time of presentation CNS signs Renal failure Hepatic dysfunction Fever Purpura Decreased platelets Creatinine increase AST ⁄ ALT increase LDH increase Hyaline thrombi Post-partum improvement HELLP >37 weeks variable variable definite nil nil mild–moderate mild increase mild +– yes TTP mid-trimester severe mild nil present severe severe mild no change marked ++ nil HUS postpartum rare severe nil nil usually nil usually moderate large no change marked ++ nil Other causes of thrombocytopenia in pregnancy HELLP = ‘Haemolysis.. gestational age of the fetus..... A lower limit of 100 · 109... Several studies have attempted to address the issue of the risk of epidural haematoma when the platelet count is between 50 and 100 · 109. there is laboratory evidence of disseminated intravascular coagulation caused by decreased hepatic synthesis of antithrombin... whereas reduced antithrombin concentrations are present in patients with pre-eclampsia or HELLP.... ALT = alanine aminotransferase...... epigastric and right upper quadrant pain.... AST = aspartate aminotransferase.. Ninety percent of cases of HUS occur in the postpartum period (mean = 26 days after delivery) [50].... Pregnant women with Type IIb von Willebrand disease may develop thrombocytopenia.......... nausea.. Elevated Liver enzymes...... There are eight reports of spinal haematomas following obstetric epidural analgesia ⁄ anaesthesia in the literature but some of these are questionable [9... helmet cells.and La-antibodies [52].... HIV infection should be considered in any thrombocytopenic patient with risk factor [55]..... 59. The high fetal loss associated with the antiphospholipid syndrome is caused by recurrent thrombosis of the placental and decidual blood vessels.P... features of microangiopathic haemolysis such as anaemia.. coagulopathy and electrolyte imbalances.......... reticulocytosis and polychromasia. associated obstetric complications.... Low Platelets’...... 57]......... and have an increased risk of thromboembolism compared with those who lack these antibodies. Burr cells.... pages 255–264 ....... increased bilirubin and lactate dehydrogenase.... cholestatic liver abnormalities... Chronic renal failure and hypertension are long-term complications associated with HUS (Table 2). fetal loss or associated pre-eclampsia [53].... decreased haptoglobin......... Kam et al. TTP. .. hypoglycaemia and decreased levels of fibrinogen and antithrombin...... These women present with malaise.... are present in TTP and HUS.......... C..... coagulation status... Remission can be achieved by plasma exchange in 75% of pregnant and non-pregnant patients with TTP....... The risk of epidural haematoma in the general population is estimated to be 1 in 150 000 after epidural analgesia [56]. In most patients with TTP and HUS..l)1 for platelet count is suggested as ‘safe’ for performing an epidural blockade. The course of TTP and HUS does not improve following delivery of the fetus.. plasma antithrombin concentrations are normal. The incidence of epidural haematoma is 0......

is not considered to be reliable to determine the safety of epidural catheter placement because of wide observer variation.9 gl)1) and it was concluded that these tests are unnecessary in clinically normal parturients....l)1 is safe for surgery and neuraxial blockade. The authors also reported that the percentage of women with platelet count values <100 · 109.84..... over a 3-year period.....Anaesthesia...........4% (11 ⁄ 797) between blood sampled during the 9th month of pregnancy and that obtained in labour.l)1 increased from 0. is caused by in vitro platelet clumping when EDTA is used as the anticoagulant.. r = )0. 261 .. In another study of TEG in normal pregnant women and in women with preeclampsia... A survey of American anaesthetists reported that 66% in academic practice and 55% of those in private practice would place an epidural anaesthetic when the platelet count is between 80 · 109. TEG variables and bleeding time in 49 parturients with pre-eclampsia. In a study of 2929 parturients. called ‘closure time’.......l)1 received epidural anaesthesia......l)1) and was associated with adequate clot formation produced by thromboelastography.... termed as pseudo-thrombocytopenia.78.l)1 [62]........ However.. In a study of 797 women.. and platelets.. However.....l)1 is required [71]. there was a correlation between platelet numbers and PFA-ADP closure time (normal range 71–118 s) particularly when the platelet count was less than 50 · 109...... In a study of platelet function during pregnancy using the PFA-100 in patients with thrombocytopenia associated with preeclampsia. Platelet activation and aggregation occurs on the membrane.. pages 255–264 P. Coagulation tests performed several weeks before delivery are not reliable in predicting coagulation abnormalities during labour [67]..... It is affected by technical (length and size of cut..l)1 (95% confidence limits....04)......... p = 0.......... Further evaluation of the PFA-100 in pregnant women with platelet counts of less than 50 · 109.........5% (3 ⁄ 797) to 1. r = )0...l)1 safely received epidural anaesthesia [63]. The thromboelastogram (TEG) measures whole blood clotting. fibrinogen... 61].. The bleeding time test... factitious platelet counts due to laboratory artefacts must be ruled out by reviewing the peripheral blood film using a citrated blood sample..... and the interactions between the coagulation cascade.l)1 [64]... 24]. occlusion pressure) and patient (ethnicity. prothrombin time and the activated partial thromboplastin time were normal in all patients including those with low platelets and plasma fibrinogen concentrations (<2. through which a central aperture is cut into the membrane covered with collagen and epinephrine or collagen-ADP...02..l)1 had a normal MA... 59. A..... which indicated a normal clot [69]. resulting in the occlusion of the aperture and interruption of blood flow [70]. Aggregometry (measures platelet aggregation in response to specific agonist such as ADP and epinephrine) and flow cytometry (measures platelet activation and aggregation) are not practical clinical tests because they are time-consuming and require technical expertise.. Æ retrospective studies have suggested that epidural anaesthesia may be safely undertaken when the platelet count is <100 · 109. It is difficult to draw firm conclusions about the reliability of TEG to predict which patients might develop epidural haematoma from these studies because few patients with platelet counts <75 · 109....l)1 [2.... Most haematologists suggest that a platelet count >50 · 109...... . Kam et al. Orlikowski measured platelet count. and is due to adhesion of platelets to the periphery of neutrophils in the presence of platelet agglutinins (IgG or IgM) [65].. The PFA-ADP closure times were normal in healthy patients...... The PFA-100 platelet function analyser evaluates primary coagulation under high shear stress by measuring the time required for whole blood to occlude an aperture in a membrane coated with collagen and the platelet agonists.. A 800-ll sample of citrated blood... simple point of care assessment of platelet aggregation. epinephrine (PFA-EPI)... no complications associated with regional anaesthesia were recorded in the 24 women who had a platelet count <100 · 109.... or adenosine diphosphate (PFA-ADP)...l)1 [71]. An MA of 53 mm correlated with a platelet count of 54 · 109.. suggesting that PFA-EPI may give false positive values.. 2004...l)1... all patients with a platelet count >75 · 109.. 40–75 · 109..l)1. the PFA-EPI closure times increased in six otherwise healthy patients. The test takes approximately 7 min.... a simple bedside test that evaluates the quality and quantity of platelets..... k time and maximal amplitude (MA) have a strong Ó 2004 Blackwell Publishing Ltd correlation with platelet count (k time ) platelet count <100 · 109.... etc.. maintained at 37 °C.. 30 parturients who had platelet counts ranging from 69 to 98 · 109. The Platelet Function Analyser (PFA-100) may offer a rapid.. hypercholesterolaemia... TEG does not measure initial platelet adhesion to exposed collagen in the damaged vessel wall... C..l)1 should not be denied regional anaesthesia [68].) factors [66]. Thrombocytopenia in the parturient ........... This artefact.... Haemostasis is initiated by platelet adhesion to damaged vessel wall and the main disadvantage of all laboratory platelet function tests is that they do not measure the interaction between platelet and the vascular endothelium.. Before carrying out further investigations to determine the cause of thrombocytopenia..... diabetes.l)1 and 100 · 109..... is aspirated into stainless steel capillaries...... MA ) platelet count <100 · 109.... The thromboelastography variables....... p = 0.. The authors suggested that patients with platelet counts greater than 75 · 109.. provided platelet function is normal [5...... Beilin and colleagues reported that.

... Maternal and fetal platelet activation in normal pregnancy... Mammen EF.. Journal of Obstetrics and Gynaecology 1978. Acta Obstetricia et Gynecologica Scandinavica 2000. 16 Shehata N. Eddelman KA.. 2nd edn.. American Journal of Obstetrics and Gynecology 1990. Riikonen S.. Crawford J. 17 Morrison R. Blomback M. Gatti L. Fibrin degradation products in normal and abnormal pregnancy and parturition..... McNicols GP. 3 Letsky E.... 2: 564–7.... American Journal of Obstetrics and Gynecology 1996...... 20 American College of Obstetrics and Gynecology Committee on Practice Bulletins.. Maternal thrombocytopenia: a population based study. Exterman P. Mammen E.. Crosignani PG.. Davidson JF. Haemostasis in pregnancy. Extermann P... Obstetrics and Gynecology 2000. Incidentally detected thrombocytopenia in healthy mothers and their infants... Farag A... 59..... Gianotti GA.. Bottoms S. Pseudo-thrombocytopenia must be excluded.... American College of Obstetrics and Gynecology Practice Bulletin. The entire clinical presentation of the patient must be considered when deciding on the appropriate choice of anaesthesia. Specific questions about medications that might interfere with platelet numbers and function should be asked.. Platelet count at term pregnancy: a reappraisal of the threshold. de Moerloose P.. Farag A. Æ Large prospective studies with an estimated sample size of >200 000 patients are required to definitively determine whether it is safe to place an epidural or spinal anaesthetic in patients with a platelet count <100 · 109..... 18 Nicolini U. during delivery and in the puerperium.. Walker W.. Gestational thrombocytopenia.. Chamberlain G. 83: 65–9...P. 67: 117–22.... 42: 327–34.. Lowe GDO.. 79: 744–9... 174: 1014–8.. Douglas AS... British Medical Journal 1970. 162: 1158–63.. 80: 2697–714. Kam et al. London: Farrand Press. 23 Boehler F. 346: 13–25. 11 Douglas JT... Antiplatelet antibody testing in thrombocytopenic pregnant women...... Douglas AS. International Journal of Gynaecology and Obstetrics 1999..... Plasma fibrinopeptide A and beta-thromboglobulin in pre-eclampsia and pregnancy hypertension. Kelton JG.... Haemostatic mechanism in the uterine circulation during placental separation. The haematological system... A physical examination of the patient should include looking for evidence of bruising and bleeding at venepuncture sites or petechiae at the blood pressure cuff site.. Obstetrics and Gynecology 1990.... Prentice CRM.. 22 Cines DG..... .. British Medical Journal 1970... Van Kessel PH. 12 Bonnar J. Blood 1992.... Immune thrombocytopenic purpura. Thrombocytopenia in pregnancy. Lind T.. Campagnoli C. 319: 142–5.. Thrombosis and Haemostasis 1982. Pidgeon CF. Bottoms S. 2: 200–3. Platelet values during normal pregnancy.. Kelton JG. A decreasing platelet count is considered a contraindication to neuraxial blockade. 4 Gerbasi FR.. Douglas AS.. 2 McCrae KR..... 21 Lescale KB..... 85: 33–6.......... Hohlfeld H. C. 162: 731–4. de Moerloose P. Maternal antiplatelet antibodies in predicting risk of neonatal 262 Ó 2004 Blackwell Publishing Ltd .... 7 Gerbasi FR. 75: 385–9. 1.. Thrombocytopenia in the parturient Anaesthesia.... 21: 141–6. 1991: 39–41... spinal anaesthesia may be safer. A soft flexible catheter that is less likely to puncture blood vessels is preferred if an epidural anaesthetic is undertaken [66].. Platelet lifespan in normal pregnancy as determined by a non radioisotopic technique. Increased intravascular coagulation associated with pregnancy.....l)1 [63]..... ed. 10 Wallenburg HCS. In: Morgan BM... New England Journal of Medicine 2002.... In: Hytten F.... Blanchette VS.. Thrombosis and Haemostasis 1985. Shah M. 2004.. Kelton JG.... Careful monitoring of the patient in the postpartum period to detect early signs and symptoms of an epidural haematoma should be undertaken. Pregnancy associated thrombocytopenia: pathogenesis and management.. British Medical Journal 1969. Guarneri D... Obstetrics and Gynecology 1994....... Hepinstall S.. Platelet behaviour in normal pregnancy.. 8 Boehlen F.. McNicol GP.. It is important to ensure that there is no clinical evidence of bleeding and that the platelet count is not decreasing when epidural catheter placement is contemplated. When considering regional anaesthesia in patients with thrombocytopenia. Schreiber AD.. 9 Gill PR.. Perneger TV. 47: 54–5.... British. Consumptive coagulopathy associated with placental abruption and other conditions must be ruled out. Thrombocytopenia at delivery: a prospective survey of 6715 deliveries.. General anaesthesia for urgent Caesarean section becomes necessary if coagulation is abnormal or there is bleeding... Gynecologic and Obstetric Investigation 1981.. pages 255–264 ... 15 Burrows RF. Hohlfeld P. New England Journal of Medicine 1988.. Samuels P. 1987: 189–207. 6 Hellgren M. 95: 29–33.. Kekomaki R. Foundations of Obstetric Anaesthesia. eds...... American Journal of Obstetrics and Gynecology 1990.. A manual platelet count is more accurate in patients with recent thrombocytopenia because automated counters are not reliable at low platelet counts. Burrow RF... Cines DB.. 19 Burrows RF. MacPherson M.. 5 Letsky E. Clinical Obstetrics and Gynecology 1999. McNicol GP. Oxford: Blackwell Scientific Publications...... Studies on blood coagulation and fibrinolysis in pregnancy..... Teramo K.... pregnancy complicated by essential hypertension and pregnancy induced hypertension. 54: 607–11. A. et al.. References 1 Sainio S....... British Journal of Obstetrics and Gynaecology 1985. especially in dynamic conditions such as pre-eclampsia and ITP [63]. Changes in hemostasis activity during delivery and the immediate postpartum period. 13 Bonnar J. 3: 137–40. Normal conditions. 14 Bonnar J... Clinical Physiology in Obstetrics........ Coagulation and fibrinolytic mechanisms during and after normal childbirth.. 92: 480–5.

... Steinberg AD. Roberts JM. Hauth J. Weiner CP. Blood 1996. Provost TT. New England Journal of Medicine 1998. Chritianens ML... Contemporary concepts of the pathogenesis and management of pre-eclampsia. Levy GG.. American Journal of Pathology 2002........ a reappraisal of management.Anaesthesia. Sibai B.. Better maternal outcomes are achieved with postpartum HELLP. 86: 220–9.. Journal of Rheumatology 1987... Zhou Y.. 187: 233–8.. Wilson WA. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Zemel MB.. et al... American Journal of Obstetrics and Gynecology 1997.... 36: 95–102... Association of thrombocytopenia and delivery method with intraventricular haemorrhage among very-low-birth-weight. Fetal thrombocytopenia and its relation to maternal thrombocytopenia. Redman CWG.. Files JC. Sweet RL. New England Journal of Medicine 1998. Nieuwenhus HK..... Hedriana HL.... American Journal of Obstetrics and Gynecology 2002. Harley JB. Woo K.... 94: 41–7.. Thrombotic microangiopathy in pregnancy and the post partum period... International Journal of Gynecology and Obstetrics 1991.. Relationships between severe neonatal thrombocytopenia and maternal characteristics in pregnancies associated with autoimmune thrombocytopenia... Annals of Internal Medicine 1977...... Gill KK...... . Guidelines on the investigation and management of thrombocytopenia in pregnancy and neonatal alloimmune thrombocytopenia. Preeclampsia is associated with abnormal expression of invasive cytotrophoblasts..... Koike T. 1101–17. Morrison JC. 2004... Obstetrics and Gynecology 2002. elevated liver enzymes and low platelets syndrome... New England Journal of Medicine 1990. Branch DW.. 70: 334–8. Payne SD... 88: 3–40. Æ 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 thrombocytopenia. Schenker JG... Hunter DJ. Molecular and Cellular Endocrinology 2002. Katz VL. Letsky EA. Perry KG. Esplin MS. Post partum plasma exchange for atypical preeclampsia as HELLP (hemolysis... Kelton JG. American Journal of Obstetrics and Gynecology 1995.. Billett HH. 24: 119–29. 103: 397–401. Kelly TF. A....... Regulation of trophoblast invasion. Obstetrics and Gynecology 1999.. Journal of Clinical Investigation 1993. Gharavi AE. Selection of delivery methods in pregnancies complicated by autoimmune thrombocytopenia: a decision analysis... Burrows RF. Placenta 1991. Nature 2001. Cefalo RC.. C. Burrows RF. elevated liver enzymes and low platelet count-complicating pre-eclampsia ⁄ eclampsia. Macones GA...... Lian EC.... Blake PG... Seminars in Hematology 1987. British Journal of Haematology 1996. Comparison of platelet counts in first and second newborns of mothers with immune thrombocytopenic purpura... et al........ Obstetrics and Gynecology 1987.. Immune thrombocytopenic purpura in pregnancy. International consensus statement on preliminary classification criteria for Ó 2004 Blackwell Publishing Ltd 263 . Martin JN... Resnick R.. 91: 950–60. Zhou Y.. Much ado about nothing? American Journal of Obstetrics and Gynecology 1990. 14: 199–205. George JN. Damsky CH.. Watson R.. 177... Chiu K. Godelieve V. pages 255–264 P... et al.. Perry KG.. Robinette L. Idiopathic thrombocytopenic purpura.. Maternal characteristics and risk of severe neonatal thrombocytopenia and intracranial hemorrhage in pregnancies complicated by autoimmune thrombocytopenia. British Journal of Haematology 1998. Caritis S. 162: 311–6.. Antibodies to von Willebrand factor cleaving protease in acute thrombotic thrombocytopenic purpura. National Institute of Child Health and Human Development network of maternal-fetal medicine units: Low dose aspirin to prevent pre-eclampsia in women at high risk. Thrombocytopenia in the parturient . Kaha DJ..... Roberts JM.. Reubinoff BE.. a practice guideline developed by explicit methods for the American Society of Hematology. Vascular endothelial cell growth factor ligands and receptors that regulate human cytotrophoblast survival are dysregulated in severe 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 pre-eclampsia and hemolysis. et al..... Miller RE. Stamilio DM.. et al. Obstetrics and Gynecology 1991. Martin JN... The HELLP Syndrome (hemolysis. Management of idiopathic thrombocytopenic purpura in pregnancy. 329: 1436–66. et al... 78: 578–83.. Altered platelet calcium metabolism as an early predictor of increased peripheral vascular resistance and pre-eclampsia in urban black women.. Journal of American Medical Association 2002.. 90: 546–52. Woolf SH. 413: 488–94.. Greaves M.. Richardson DK... elevated liver enzymes and low platelets). 95: 21–36.. From normal implantation to pre-eclampsia... New England Journal of Medicine 1993.. HELLP syndrome ) a syndrome of hemolysis... 59.. Tsai HM. Lian ECY. Bussel JB... 42: 360–8... Management of idiopathic thrombocytopenic purpura during pregnancy. Berry S. Yagel S. American Journal of Obstetrics and Gynecology 1997... 177: 149– 55.. 339: 1585–94.. Laros RK. Budman DR... Zemel PC..... Goldman-Wohl D... American Journal of Obstetrics and Gynecology 1975. Blake PG. Kelton JG. 37: 275–83...... Valat AS. Obstetrics and Gynecology 1997. Hematologic aspects of systemic lupus erythematosus.. Seminars in Hematology 2000.... Diagnosis and management of thrombotic microangiopathies during pregnancy. 323: 434–8......... 186: 109–16.. 160: 1405–23....... elevated liver enzymes and low platelets).. The neonatal lupus erythematosus syndrome.. May WA. 338: 701–5.. Cook RL. Roskob GE.. McMaster M.... 12: 301–8. Sibai BM... et al. Clinical Obstetrics and Gynecology 1999. Nichols WC. A prospective study investigating the mechanism of thrombocytopenia in pre-eclampsia... Current topic: pre-eclampsia and the placenta. Kam et al.. Gaither KK... Kelton JG. Andrew M.... Lain KY. 287: 3183–6. Moore TR.... 172: 1107–12. Devos P. Moore A... Caulier MT. Norman PH..... 122: 182–6. Fisher SJ.. 93: 169–73..

... 83: 735–41. 42: 1309–11... Iresdedt L.. British Journal of Anaesthesia 2001.. Raskob GE. Haddad EM..000 and 98. Kam et al.. 85: 385–90. Wright WC.P... 77: 157–61. Tan IKS. Thrombocytopenia in the parturient Anaesthesia. Huh C.. Rosenblatt RM.. Kua JSW... Epidural anaesthesia in pregnant women with low platelet counts. 24: 195–202. 87: 650–2.. 264 Ó 2004 Blackwell Publishing Ltd . Æ 54 55 56 57 58 59 60 61 62 definite antiphospholipid syndrome. Stone JJ. pages 255–264 ... Comp PC. Safe epidural analgesia in thirty parturients with platelet counts between 69... Main E.... Anesthesia and Analgesia 1997. Assessment of changes in coagulation in parturients with pre-eclampsia using thromboelastography. Anaesthesia 1999.... Obstetrics and Gynecology 1988. Musclow E.. Rottman RL. A systematic review of published case reports. 40: 340–5. Rasmus KT... Anesthesiology 1999. Hemostasis and epidural anaesthesia. Spinal subdural haematoma in a parturient after attempted epidural anaesthesia... 1: 51–4....... Santi TM.. Hamza J. eds.. 9: 99–124.. 54: 350–4. MacDonald D.. Rocke DA. Anesthesia for Obstetrics. McGaraghan A.. Anesthesia and Analgesia 1996..... Dahlgren G. Nathan N.. 70 Mammen EF..... 66 Douglas MJ. British Journal of Anaesthesia 1996... Neurological complications in obstetric regional anaesthesia. Bromage PR. Halpern SH. George JN... Yuen TST..... 65 Chrisopoulos CG.... C.. et al..... Padakandla UB... Unrecognised thrombocytopenia and regional anaesthesia in parturients: a retrospective review.. Kilpatrick S... 68 Orlikowski CEP..... Drug-induced thrombocytopenia. Levinson G. 71 Vincelot A. 129: 886–90. Laros RK....... 67 Simon L... Murray WB... et al. British Journal of Haematology 1994. Freedman J.......000 ⁄ lL. Zahn J.. Sacquin P.. 87: 890–3... Lie LM.. Seminars in Thrombosis and Hemostasis 1998....... International Journal of Obstetric Anaesthesia 2000.. 184: 229–30.... 63 Beilin YM. 2004. 90: 3485–90. the parturient and regional anesthesia.. 3rd edn. Annals of Internal Medicine 1998. American Journal of Obstetrics and Gynecology 2001. Neurologic Complications of regional anaesthesia for obstetrics. Gosselin R................. Papsin F. Letsky EA.. Julia A.. Hambleforn J... Rolbin SH.... Philip J. Obstetrics and Gynecology 1989.. et al....... Collet D.. 59. International Journal of Obstetric Anaesthesia 1991.. 71: 918–20.. Platelet function during pregnancy: an evaluation using the PFA-100 analyser.. Abbott D... 10: 113–20... Leibowitz AB... Grandchamp P.. 69 Sharma SK.......... British Journal of Anaesthesia 1997... . Shah SR. 64 Beilin Y..... 73: 943–6..... Kotelko DM. Canadian Journal of Anaesthesia 1993... Maternal and fetal outcomes in pregnancies affected by Von Willebrand disease type 2...... Landers DF. Burlingame J.. Machin SJ. Whitten CW.. Pre-anaesthetic assessment of coagulation abnormalities in obstetric patients: Usefulness... Bodian CA. Comerford M.. Thromboelastography changes in pre-eclampsia and eclampsia. Platelets. Baltimore: Williams & Wilkins. 1993: 443–4....... A new type of pseudothrombocytopenia: EDTA-mediated aggregation of platelets bearing FAB fragments of a chimeric antibody..... Spinal haematoma following epidural anaesthesia in a patient with eclampsia... A.... Lao TT....... PFA-100: a new method of assessment of platelet function.... timing and clinical implications... In: Schnider SM. Loo CC... 78: 678–83. Mehaddi Y.. International Journal of Obstetric Anaesthesia 2001. Arthritis and Rheumatism 1999.. Practice patterns of anesthesiologists regarding situations in obstetric anesthesia where clinical management is controversial..