Pregnancy-associated Thrombocytopenia Research Articles

Evaluation of Women with Pregnancy Associated Thrombocytopenia

Objective: To determine frequency of thrombocytopenia among pregnant women Study Design: Descriptive cross sectional study. Place and Duration of Study: Department of Gynaecology & Obstetrics from 1st May 2018 to 30th November 2018. Methodology: One hundred and fifty seven pregnant women of reproductive age of 15-45 years, who were normotensive without any malarial parasite or platelet aggregation seen on peripheral film were included while women with previous pregnancy with history and prior record of thrombocytopenia, on steroids, NSAIDS, or who went through splenectomy were excluded. Selected cases were thoroughly examined investigated for all possible causes. Results: The average age of 32.57±6.63 years, among these 21 [13.37%] were primiparous, 78 [49.68%] multiparous and 58 [36.94%] grand multiparous. Mean gestational age was 36.65±1.82 weeks, Mean Weight was 73.06±16.09 kg, mean height was 161.99±9.96 cm and mean BMI was 27.87±6.25 kg/m2. Conclusion: Thrombocytopenia among pregnant women with 33% prevalence observed. Key words: Pregnancy associated thrombocytopenia (PAT), Pregnancy, Frequency

English

Introduction Thrombocytopenia, or a low blood platelet count, is encountered in 7–8% of all pregnancies1. It is the second most common blood disorder in pregnancy2,3. The first blood disorder is anaemia3. Platelets are non-nucleated cells derived from megakaryocytes in the bone marrow and normally live in the peripheral circulation for as long as 10 days. Platelets play a critical initiating role in haemostatic system1,4. The normal range of platelets in non-pregnant women is 150 000– 400 000/μL. Average platelet count in pregnancy is decreased. Change in platelet count is due to haemodilution, increased platelet consumption and increased platelet aggregation driven by increased levels of thromboxane A2. Thrombocytopenia can be defined as platelet count less than 150 000/μL or platelet count below the 2.5th percentile for pregnant patients (116 000/μL)1. Classification of thrombocytopenia in pregnancy is arbitary and not necessarily clinically relevant. Mild thrombocytopenia is 100 000– 150 000/μL, moderate thrombocytopenia is 50 000–100 000/μL and severe thrombocytopenia is less than 50 000/μL. The pathophysiology of gestational thrombocytopenia (GT) is unknown. It usually develops in the third trimester, detected incidentally, pati ents are asymptomatic with no prepregnancy history of low platelets or abnormal bleeding, it is mild thrombocytopenia (counts more than 70 000/μL)5–9. GT accounts for almost threefourths of all cases of thrombocytopenia2,10. Mode of delivery is determined by obstetric/maternal indications. Platelet counts normalize within 2–12 weeks following delivery10–12. No pathological significance for the mother or foetus is noted. No risk for foetal haemorrhage or bleeding complications is observed13–17. A low platelet count can also be associated with preeclampsia, HELLP syndrome or idiopathic thrombocytopenic purpura (ITP)18–23. The differential diagnosis between mild ITP and GT is very difficult during pregnancy5,19. ITP accounts for only approximately one case of thrombocytopenia per 1000 pregnancies and 5% of cases of pregnancy-associated thrombocytopenia, it is the most common cause of significant thrombocytopenia in the first trimester24–27. Women with ITP often have a history of bleeding complications and have thrombocytopenia on a prepregnancy platelet count16,28. We present this rare case of GT in a pregnant 30-year-old woman.

New-onset immune thrombocytopenic purpura (ITP) in pregnancy

ObjectiveImmune thrombocytopenic purpura (ITP) is a rare but important cause of thrombocytopenia in pregnancy, accounting for approximately 5% of cases of pregnancy-associated thrombocytopenia and affecting 1-2 in 1000 pregnancies.1 Its...

Pregnancy-Induced Thrombocytopenia in Pseudo-Von Willebrand Disease

Abstract 4658Platelet-type von Willebrand disease, or pseudo-VWD, is a rare congenital platelet disorder due to a mutation in the glycoprotein 1b alpha receptor. This results in increased binding of normal VWF to platelets, leading to platelet aggregation and intermittent thrombocytopenia. Although the mechanism is similar to type IIb VWD, this gain of function mutation affects the platelet, rather than plasma VWF.We report a patient with pseudo-VWD who developed progressive thrombocytopenia during pregnancy. She was initially seen at 10 weeks gestation, when the platelet count was 143 × 109 /L (figure 1). As the pregnancy progressed, the platelet count decreased, accompanied by an inverse rise in VWF antigen and activity, factor VIII activity, and an increase in high molecular weight (HMW) multimers (figure 2). The VWF activity to antigen ratio remained abnormal at all times. At the time of delivery, the platelet count reached a nadir of 36 × 109/L. Post-partum, the platelet count normalized to 185 × 109/L with a concomitant fall in VWF antigen and activity levels. VWF multimer analysis after delivery showed an absence of high molecular weight multimers. [Display omitted] FIGURE 2Weeks GestationPlatelet count (×109 /L)VWF antigenVWF activityFactor VIIIPlatelet aggregationVWF multimers1014381%35%88%↑ ristocetin 0.6normal3654144%57%205%not donenormal+15 post-partum18555%19%49%not doneHMW multimers absentThe likely etiology of the progressive decrease in the platelet count is secondary to the physiologically stimulated rise in VWF levels during pregnancy. With rising VWF levels, the abnormal platelet GP1b alpha receptor binds VWF, resulting in platelet-VWF aggregates with subsequent clearance. Transfusion of normal platelets would be the only way to correct the abnormality. Our patient, a Jehovah's Witness, would not accept platelet transfusion if it became necessary. She underwent an uncomplicated cesarean section for obstetric indications.Our patient's family was the subject of the landmark article initially describing this condition (Weiss HJ, Meyer D, Rabinowitz R, et al. Pseudo- von Willebrand's disease: An intrinsic platelet defect with aggregation by unmodified human factor VIII/von Willebrand factor and enhanced adsorption of its high-molecular-weight multimers. N Engl J Med 1982; 306:326-333). This patient is the 2-year old who was not tested when the family was initially evaluated. To our knowledge, this is the first reported case of pregnancy-associated thrombocytopenia in a patient with pseudo-VWD. Disclosures:No relevant conflicts of interest to declare.

Pregnancy-Associated Thrombocytopenia Revisited: Assessment and Follow-Up of 50 Cases

AbstractThrombocytopenia detected during pregnancy addresses the issue of its mechanism and of the possible occurrence of neonatal thrombocytopenia. To further investigate these issues, 50 women referred to us because of thrombocytopenia detected during pregnancy (platelet count, <150 × 109/L), were extensively studied, as well as their offspring. Among these thrombocytopenic women, we used the threshold of 70 × 109/L to differentiate between mild and severe thrombocytopenia. Whatever the severity of thrombocytopenia, we found biological features of an autoimmune disorder in 48% of the women, and chronic thrombocytopenia in 55%. A familial thrombocytopenia was evidenced in 1 case. These 50 women gave birth to 63 neonates, among whom 24 were thrombocytopenic, either at birth or during the first week of life. Neonatal thrombocytopenia could only be predicted in multiparous women, on the basis of previous neonatal thrombocytopenia in older siblings, and/or when maternal platelet life span study, performed before pregnancy, had evidenced an autoimmune thrombocytopenia (AITP)-like profile. These results suggest that, in case of pregnancy-associated thrombocytopenia, familial and immunological studies, combined with postdelivery iterative platelet counts, should be performed to properly characterize the thrombocytopenia. Moreover, the platelet count of the neonate should be carefully assessed at birth and during the following days, a platelet life span study should be performed after delivery in the mother, because these two parameters are likely to bring valuable information regarding the forthcoming pregnancies and the risk of neonatal thrombocytopenia.

Pregnancy-Associated Thrombocytopenia Revisited: Assessment and Follow-Up of 50 Cases

Thrombocytopenia detected during pregnancy addresses the issue of its mechanism and of the possible occurrence of neonatal thrombocytopenia. To further investigate these issues, 50 women referred to us because of thrombocytopenia detected during pregnancy (platelet count, &lt;150 × 109/L), were extensively studied, as well as their offspring. Among these thrombocytopenic women, we used the threshold of 70 × 109/L to differentiate between mild and severe thrombocytopenia. Whatever the severity of thrombocytopenia, we found biological features of an autoimmune disorder in 48% of the women, and chronic thrombocytopenia in 55%. A familial thrombocytopenia was evidenced in 1 case. These 50 women gave birth to 63 neonates, among whom 24 were thrombocytopenic, either at birth or during the first week of life. Neonatal thrombocytopenia could only be predicted in multiparous women, on the basis of previous neonatal thrombocytopenia in older siblings, and/or when maternal platelet life span study, performed before pregnancy, had evidenced an autoimmune thrombocytopenia (AITP)-like profile. These results suggest that, in case of pregnancy-associated thrombocytopenia, familial and immunological studies, combined with postdelivery iterative platelet counts, should be performed to properly characterize the thrombocytopenia. Moreover, the platelet count of the neonate should be carefully assessed at birth and during the following days, a platelet life span study should be performed after delivery in the mother, because these two parameters are likely to bring valuable information regarding the forthcoming pregnancies and the risk of neonatal thrombocytopenia.

Relationships between severe neonatal thrombocytopenia and maternal characteristics in pregnancies associated with autoimmune thrombocytopenia.

In pregnant women with antecedents of autoimmune thrombocytopenia (AITP), no predictive factor for severe fetal thrombocytopenia has been identified. We evaluated the relationships between the course of the maternal disease before and during pregnancy and the risk of severe fetal thrombocytopenia, in 64 pregnant women with known chronic AITP antecedents, over a 12-year period. 28 pregnant women had undergone splenectomy before pregnancy and 17 experienced severe thrombocytopenia (< 50 x 10(9)/l) during pregnancy (monthly determination). Eight infants presented with severe thrombocytopenia at birth (12.5%), and four in the following days (6.25%). No severe haemorrhage was observed. Severe thrombocytopenia at birth was present in 57% (CI 95% 18-90%) of the infants born to mothers with severe pregnancy-associated thrombocytopenia and splenectomy antecedents, and in 0% (CI 95% 0-15%) of the infants born to mothers who presented none of these antecedents (P=0.001). In thrombocytopenic mothers the infant platelet counts at birth were positively correlated to the nadir maternal platelet count during the index pregnancy (r=0.42, P=0.0075). These results suggest that severe autoimmune disease is a risk factor for severe fetal thrombocytopenia, and that pregnant women with no antecedent of splenectomy nor severe thrombocytopenia during pregnancy have a very low risk of severe fetal thrombocytopenia.

Occurrence of Early Pregnancy-Associated Thrombocytopenia in Splenectomized Rabbits.

The occurrence of early pregnancy-associated thrombocytopenia (EPAT) in adult female rabbits was examined in the present study. The rabbits were divided into 5 groups: (i) 5 rabbits were superovulated with follicle stimulating hormone (FSH) and human chorionic gonadotropin (hCG) and mated, but the embryos were not recovered; (ii) 6 rabbits were superovulated and mated, and the embryos were recovered; (iii) 8 rabbits were splenectomized and mated, and the embryos were recovered; (iv) 6 rabbits were splenectomized and injected with hCG; and (v) 3 control rabbits underwent sham operations and they were injected with hCG. In each case, blood (2 ml) was obtained by venipuncture from the marginal ear vein from the day of hCG injection to the day of embryo collection. A significant change of peripheral platelet concentration (PLT) was characterized either by a decrease or by an increase of >20% compared with the value of the initial sampling time. The proportions of rabbits which displayed a significant change in PLT were 80% (4/5) in Group i, 83% (5/6) in Group ii, 100% (8/8) in Group iii, 83% (5/6) in Group iv and 67% (2/3) in Group v(P>0.05). In Groups i and ii, 91% (10/11) of rabbits showed an increase of PLT. In Group iii, 75% (6/8) of rabbits showed a decrease of PLT (EPAT). In Groups iv and v, although each rabbit showed a decrease of PLT, the PLT patterns were variable. Effects of group (interaction of treatment/condition × pregnant status) and pregnant status on PLT were significant (P<0.0004 and P<0.0003 respectively). No effect of time after hCG injection on PLT was detected. Significant differences of PLT were observed only between Group i or ii and other groups, when least square mean was compared with a variance of time after hCG injection. From the results of the present study, splenectomy for the pregnant rabbits was requisite for an occurrence of EPAT. Also, the results suggest that EPAT does not occur in normal rabbits. Observations in splenectomized rabbits suggest that platelet activation may be occurring in early pregnancy but not to a sufficient degree to cause measurable thrombocytopenia in peripheral blood.

Possible Role of Platelet-Activating Factor in Embryonic Signaling during Oviductal Transport in the Hamster1

Hamster embryos enter the uterus in pregnant females nearly one day earlier than unfertilized eggs in cycling females. The hypothesis that a substance derived from eicosanoids is released by the embryos, but not by oocytes, to hasten their transport to the uterus was tested by examining the effects of indomethacin, nordihydroguaiaretic acid (NDGA), platelet-activating factor (PAF), and PAF antagonists on egg transport in the hamster. Administration of indomethacin had no effect on embryo transport, whereas administration of NDGA delayed the transport of eggs to the uterus in pregnant but not in cycling hamsters. The PAF antagonists TCV-309 and BN-52021 delayed significantly the transport of eggs to the uterus in pregnant animals, but not in cycling animals; i.e., they retarded the passage of embryos but not of oocytes to the uterus. Administration of PAF to cycling hamsters hastened the oviductal transport of ova. These data suggest that, in the hamster, the earlier passage of embryos to the uterus as compared to oocytes is mediated by PAF. Thrombocytopenia was detected in early-pregnant hamsters, and PAF-like activity was detected in spent media of two-cell through morula stage hamster embryos. These results suggest that preimplantation hamster embryos produce PAF-like activity that mediates embryonic signaling to the oviduct as well as pregnancy-associated thrombocytopenia.

Clinical relevance of gestational thrombocytopenia of &lt;100,000/μl

We identified 22 women with thrombocytopenia of < 100,000/microliters found incidentally during pregnancy and prospectively monitored their platelet count and clinical outcome for a minimum of 6 months postpartum. During the study period, four women became pregnant twice, accounting for a total of 26 pregnancies. The lowest platelet count during pregnancy was 65,600/microliters +/- 19,400 (mean +/- SD), and at delivery 84,500/microliters +/- 32,300 (P < 0.02). The thrombocytopenia was virtually asymptomatic in all patients during the pregnancy and delivery, whether vaginal or surgical. Neonatal platelet counts (n = 18) were normal (270,700/microliters +/- 69,900), and none of the newborns (n = 24) had a bleeding diathesis. Normalization of the platelet count (i.e., > 150,000/microliters) was documented in 18 patients within 1 month postpartum, in five within 3 months postpartum, and in two as late as 5 months after delivery. One woman did not recover from the thrombocytopenia and eventually developed other stigmata of an autoimmune disease. Long-term follow-up showed recurrence of thrombocytopenia in four patients: three in the context of a subsequent pregnancy and one who developed idiopathic thrombocytopenic purpura. Retrospective analysis of blood counts obtained from 12 previous pregnancies demonstrated thrombocytopenia of a similar degree to the index pregnancy. We conclude that gestational thrombocytopenia of < 100,000/microliters is clinically a benign phenomenon that can recur in subsequent pregnancies and is not accompanied by neonatal thrombocytopenia. In some cases, however, pregnancy-associated thrombocytopenia may be a manifestation of an autoimmune disease with its attendant implications for the neonate. Since the differential diagnosis between the two conditions may be difficult to establish when first encountered during pregnancy, a conservative approach emphasizing careful surveillance and guarded reassurance is justified as long as the platelet counts are > 50,000/microliters.

Pregnancy-Associated Thrombocytopenia: Pathogenesis and Management

Pregnancy-Associated Thrombocytopenia: Pathogenesis and Management

Pregnancy-associated thrombocytopenia: pathogenesis and management

Pregnancy-associated thrombocytopenia: pathogenesis and management

Early pregnancy associated thrombocytopenia as an initial response to pregnancy in cattle

This study was conducted to determine if early pregnancy-associated thrombocytopenia exists in cattle as has been demonstrated in mice and in humans. Three experiments were designed to compare peripheral platelet counts in pregnant versus nonpregnant animals. In Experiment 1 heifers (n = 25) were artificially inseminated 12 h after the onset of estrus. Peripheral platelet counts in 19 pregnant versus 6 nonpregnant heifers did not reveal any significant differences between groups after insemination. In Experiment 2 embryos were collected nonsurgically from superovulated cows (n =18) on Days 6 to 7 after estrus. Platelet counts were monitored every 12 h after the first insemination until 60 h after the second insemination. Platelet counts and the number of embryos collected nonsurgically from these superovulated donors did not show any significant correlations (P>0.05). Ten recipient heifers synchronized to donor animals received either an unfertilized ovum or a good quality embryo via nonsurgical transfer into the uterus. There were no significant reductions in platelet counts after transfer. In Experiment 3 platelet counts were monitored daily in four pregnant and five nonpregnant recipient heifers between Day 0 and Day 30 after embryo transfer on Day 8 of the cycle. The platelet counts did not reveal any significant differences between the pregnant and nonpregnant groups throughout Days 0 to 30. These results indicate that early pregnancy-associated thrombocytopenia cannot be demonstrated in cattle. Peripheral platelet counts cannot be used as an indicator of early pregnancy in cattle.

Peripheral blood platelet counts in the management of very early pregnancy failure following gamete intrafallopian transfer

Early pregnancy-associated thrombocytopenia has been described previously in the peripheral blood of in vitro fertilization (IVF) patients and is evaluated here in 26 women undergoing gamete intrafallopian transfer (GIFT). No consistent fall in platelets was seen in ongoing pregnancies. It is suggested that a fall in peripheral blood platelets in the early luteal phase may be observed only in pregnancies where more than one embryo is present.

Pregnancy-Associated Thrombocytopenia: Definition, Incidence and Natural History

We have sought to clarify the definition and importance of newly diagnosed thrombocytopenia in pregnant women by establishing an appropriate reference interval for the platelet count, and by observing the outcome in a cohort of thrombocytopenic pregnant women. The mean platelet count was lower in 2,155 healthy pregnant than non-pregnant women, and varied with race, but did not fall with increasing gestation, except in Black women. 101 of approximately 2,800 women became newly thrombocytopenic during pregnancy by conventional criteria (platelets less than 150 x 10(9)/l), without an apparent cause. Using the reference intervals established during the study, however, 24 of these women would not have been regarded as thrombocytopenic. No bleeding tendency was observed in the mothers or their infants. Maternal platelet counts became normal in the postnatal period. Thrombocytopenia occurring for the first time during pregnancy may be a different condition from auto-immune thrombocytopenia, and we suggest the term 'pregnancy-associated thrombocytopenia' (PAT). PAT does not appear to be epidemic; it does not threaten the fetus, but it cannot be distinguished from auto-immune thrombocytopenia in individual cases.

An evaluation of peripheral blood platelet enumeration as a monitor of fertilization and early pregnancy

This paper reports our data that confirm the existence of early pregnancy-associated thrombocytopenia (EPAT) in the mouse and illustrate that the phenomenon is independent of age, parity, and strain differences. This paper also provides evidence that the EPAT phenomenon is induced by a soluble factor (EPAT-factor) released by the fertilized ovum. EPAT-factor was produced in vitro by mouse embryos from the 1-cell stage to the expanded blastocyst stage. The human study involved a "blind" analysis of serum samples, collected from in vitro fertilization-treated patients, for the presence of thrombocytopenic activity. Results suggest that measurement of this thrombocytopenic activity might be useful as an index of embryo viability and might be clinically applicable for the monitoring of implantation success in in vitro fertilization programs.

Mechanistic studies of early pregnancy associated thrombocytopenia (EPAT) in the mouse.

The preimplantation period of uterine pregnancy is associated with the transient (first 4 days of gestation) expression of a state of early pregnancy-associated thrombocytopenia (EPAT), a phenomenon shown to be mediated by the embryo-derived EPAT factor, which presumably causes platelet activation and subsequent removal. We previously investigated the time course of production of EPAT factor in mouse embryo culture medium and found a correlation between the production of this factor and the in vivo platelet alterations in pregnant mice. The present paper supports the postulation that the EPAT factor and PAF-acether (a phospholipid platelet-activating factor) are related by providing data showing that PAF-acether may be responsible for the thrombocytopenia. Finally, data are presented to suggest that platelet activation, though not affecting the rate of ovulation, is important for successful ongoing pregnancy. Results suggest that the EPAT factor, produced by the fertilized egg, might act to signal uterine decidualization and/or modulate maternal immunological rejection of the implanting conceptus.

Examination of the causes of early pregnancy-associated thrombocytopenia in mice.

In mice, neither the bleeding time nor the clotting time of whole blood was different on Day 2 of pregnancy compared with pseudopregnancy. Standardization of the platelet concentration to 10(6)/microliters plasma resulted in a significant reduction in the clotting time of plasma from pregnant animals. This reduction was not due to an increase in the intrinsic or extrinsic pathways of the coagulation cascade but to enhanced platelet factor III activity, indicating increased platelet activation and consumption. Increased activation was not due to immunological recognition of the embryo because thrombocytopenia occurred after syngeneic and allogeneic matings of inbred strains of mice and also after parthenogenetic activation of ova in situ. Injection of embryo culture medium into splenectomized mice induced a significant dose-dependent thrombocytopenia. It occurred within 10 min after injection and persisted for up to 2 h. There was no reduction in platelet count when animals were injected with culture media in which unfertilized ova had been incubated. Early pregnancy-associated thrombocytopenia was caused by the production of platelet-activating factors by the fertilized eggs. The induction of thrombocytopenia by embryo culture media displayed a dose-response curve that was parallel to that of the platelet-activating factor, 1-0-alkyl-2-acetyl-sn-glycero(3)phosphocholine.