Use of therapeutic apheresis methods during pregnancy.

This review will focus on the current application of TA in pregnancy and possible aspects for future studies. It seems that scientific interest and field for further research in pregnancy is lately focused in specific removal of pathogens implicated in the physiologic mechanism of pre-eclampsia/HELLP syndrome as well as recurrent pregnancy failure.

Pregnancy-Associated Liver Diseases.

The liver disorders unique to pregnancy include hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, acute fatty liver of pregnancy, and preeclampsia-associated hepatic impairment, specifically hemolysis, elevated liver enzymes, and low platelet count syndrome (HELLP). Their importance lies in the significant maternal and fetal/neonatal morbidity and mortality. Expeditious diagnosis and clinical evaluation is critical to ensure timely, appropriate care and minimize risks to the pregnant woman and her fetus/baby. A multidisciplinary approach is essential, including midwives, maternal-fetal-medicine specialists, anesthetists, neonatologists, and hepatologists.

Conservative Treatment of Huge Hepatic Subcapsular Hematoma Complicated with Hepatic Infarction after Cesarean Section Caused by HELLP Syndrome - a Case Report and Literature Review.

Hepatic subcapsular hematoma and hepatic infarction in labor are mostly secondary to HELLP syndrome and preeclampsia. There are few reported cases with a complicated diagnosis and treatment and high mortality. Here, we present a case of a huge hepatic subcapsular hematoma complicated with hepatic infarction after cesarean section that was secondary to HELLP syndrome and the patient was treated conservatively. Further, we have discussed the diagnosis and treatment of hepatic subcapsular hematoma and hepatic infarction caused by HELLP syndrome.

[Acute Fatty Liver of Pregnancy - Case Series]. / Akute Schwangerschaftsfettleber ­ Fallserie einer seltenen Schwangerschaftskomplikation.

With a prevalence of 0,01-0,03%, acute fatty liver in pregnancy (AFLP) is a rare and dangerous complication of pregnancy and is difficult to distinguish from other, sometimes more common, pregnancy diseases such as HELLP syndrome, aHUS and TTP because of its mostly non-specific symptoms. Due to its rarity, AFLP is often not obvious to the obstetrician as a possible differential diagnosis. Yet early diagnosis and the fastest possible delivery is the only causal therapy and is important for the mortality rate. In the present manuscript, the pathophysiology, diagnosis and therapy of acute fatty liver in pregnancy are highlighted for the clinical routine based on case descriptions from three university hospitals, and reference is made to possible findings that are helpful in establishing the diagnosis. The angiogenic preeclampsia marker sFlt-1 plays a role and provides new opportunities to consider pathophysiological approaches.

Thrombotic microangiopathy during pregnancy.

Pregnancy is a high-risk time for the development of different kinds of thrombotic microangiopathy (TMA). Three major syndromes including TTP (thrombotic thrombocytopenic purpura), PE/HELLP (preeclampsia/hemolysis, elevated liver function tests, low platelets), and aHUS (atypical hemolytic- uremic syndrome) should be sought in pregnancy-TMA. These severe disorders share multiple clinical features and overlaps and even the coexistence of more than one pathologic mechanism. Each of these disorders finally ends in endothelial damage and fibrin thrombi formation within the microcirculation that fragments RBCs (schystocytes), aggregates platelets, and creates ischemic injury in the targeted organs i.e.; kidney and brain. Although the mechanisms of these severe disorders have been revealed, pregnancy-related TMA still interfaces with diagnostic and therapeutic challenges. Here, we highlight the current knowledge of diagnosis and management of these complications during pregnancy.

Is the presence of antiphospholipid antibodies a poor prognostic factor for patients with hemolysis, elevated liver enzymes, and low platelet count syndrome?

BACKGROUND: The characteristics of antiphospholipid syndrome-associated hemolysis, elevated liver enzymes, and low platelet count syndrome are poorly described, likely because of the low frequency of this combination of syndromes. OBJECTIVE: This study aimed to compare the characteristics and prognosis of hemolysis, elevated liver enzymes, and low platelet count syndrome in patients with and without antiphospholipid syndrome. STUDY DESIGN: In this multicenter, case-control study, adult women diagnosed with hemolysis, elevated liver enzymes, and low platelet count syndrome before 34 weeks' gestation and who were also tested for antiphospholipid antibodies according to international diagnostic recommendations were included. Cases labeled "HELLP-APS+" were defined as patients who fulfilled the international classification criteria for antiphospholipid syndrome; they were retrospectively recruited by screening the 672 patients with antiphospholipid syndrome in our antiphospholipid syndrome database. Control cases labeled "HELLP-APS-" were defined as patients who did not fulfill the criteria for antiphospholipid syndrome; they were retrospectively recruited from our hospital admission database. RESULTS: Overall, 71 patients were included (mean age, 30±5 years), with 23 patients in the hemolysis, elevated liver enzymes, and low platelet count syndrome with antiphospholipid syndrome group and 48 patients in the hemolysis, elevated liver enzymes, and low platelet count syndrome without antiphospholipid syndrome group. The live birth rate was significantly lower for patients with hemolysis, elevated liver enzymes, and low platelet count with antiphospholipid syndrome than for those with hemolysis, elevated liver enzymes, and low platelet count syndrome without antiphospholipid syndrome (43.5% vs 89.4%; P<.001). The patients with hemolysis, elevated liver enzymes, and low platelet count syndrome with antiphospholipid syndrome gave birth prematurely more often than the patients without antiphospholipid syndrome (24 weeks' gestation; 22.0-28.0 weeks vs 30 weeks' gestation; 27.0-33.0 weeks; P<.001). Among the patients with hemolysis, elevated liver enzymes, and low platelet count syndrome with antiphospholipid syndrome, 39% required an induced abortion owing to hemolysis, elevated liver enzymes, and low platelet count syndrome severity vs 8.5% of the patients with hemolysis, elevated liver enzymes, and low platelet count syndrome without antiphospholipid syndrome (P=.006). The intensive care unit admission rate was 61.9% in patients with hemolysis, elevated liver enzymes, and low platelet count syndrome with antiphospholipid syndrome, which was significantly higher than the rate of 27.7% in patients with hemolysis, elevated liver enzymes, and low platelet count syndrome without antiphospholipid syndrome (P=.007). None of the mothers died. CONCLUSION: Our results suggest that the presence of antiphospholipid syndrome is a poor prognostic factor for both the mother and fetus in patients with hemolysis, elevated liver enzymes, and low platelet count syndrome.

The effect of therapeutic plasma exchange on management of HELLP Syndrome: The report of 47 patients.

BACKGROUND AND OBJECTIVES: HELLP syndrome is a life-threatening condition that may potentially cause complications during pregnancy. If not diagnosed and treated quickly, HELLP syndrome may lead to serious complications both for the mother and the baby. The aim of this study was to determin the effectiveness of therapeutic plasma exchange (TPE) for treatment of Class-I HELLP syndrome. MATERIALS AND METHODS: Laboratory results from 47 patients with Class-I HELLP syndrome patients who underwent TPE between 2011 and 2020 were recorded before and after the procedure. A central venous catheter was inserted, and TPE was performed in patients who had not responded to delivery, steroid, and supportive therapy (blood products, anti-hypertensive therapy, intravenous fluid administration, and antibiotics) within 24 hours after the diagnosis of Class I HELLP syndrome according to the Mississippi Criteria. RESULTS: The average age of patients was 33 ± 4.7 years (range; 21-39 years). A mean of 5 (range; 4 to 6) TPE sessions were performed. There was a statistically significant decrease in total bilirubin, lactic dehydrogenase, aspartate aminotransferase, and alanine aminotransferase levels in all patients, whereas a significant increase in platelet count was observed (p < 0.05). Furthermore, clinical and laboratory improvement was achieved. CONCLUSION: In all patients with HELLP syndrome, a dramatically clinical and laboratory improvement occurred after TPE. Our study suggests that postpartum use of TPE within 24 hours is an efficient treatment option for Class-I HELLP syndrome.

Managing a rare complication of HELLP syndrome in Australia: Spontaneous liver haematoma in pregnancy.

Spontaneous subcapsular haematoma of the liver is a rare but life-threatening complication of pregnancy. Prevention of maternal and fetal death requires early identification and specialised management. We report three cases of spontaneous liver haematoma in pregnancy from our institution between 2011 and 2018. We conducted a systematic search of online databases using search terms, ('liver' AND 'pregnancy') AND ('haematoma' OR 'rupture') in order to present a narrative review of the literature and a systematic management framework. Our series is the first Australian report of spontaneous subcapsular haematoma in pregnancy with one fetal death in utero but no maternal deaths. Our systematic search of online databases revealed 45 similar reports in the last ten years. Individual patient data were available for 73 cases. The overwhelming majority of these reports were single cases or small case series. We estimate the mean maternal mortality rate to be 15% but fetal mortality was substantially greater than 15% (although data for neonatal outcomes was incomplete). There was one case report of liver transplantation with excellent maternal and fetal outcome. In the last five years, modern diagnostic techniques and therapeutic options have significantly reduced maternal and fetal mortality. Hepatic artery embolisation is a minimally invasive approach under guidance of imaging and is likely to achieve the best maternal and fetal outcomes. Based on our literature review, we have provided a systematic management framework for spontaneous liver haematoma in pregnancy.

Transcatheter Arterial Embolization for Spontaneous Hepatic Rupture Associated with HELLP Syndrome: A Case Report.

Background: Spontaneous hepatic rupture associated with the syndrome characterized by hemolysis, elevated liver enzymes, and a low platelet count (HELLP syndrome) is a rare and life-threatening condition, and only a few cases regarding the management of this condition through transcatheter arterial embolization (TAE) have been previously reported. Case summary: Herein, we report a case involving a 35-year-old pregnant woman who presented at 28 weeks of gestation with right upper quadrant pain, hypotension, and elevated levels of liver enzymes. Transabdominal ultrasound revealed fetal death. She required an emergency cesarean section, and hepatic rupture was identified after the fetus had been delivered. Hepatic packing and TAE were performed. The postprocedural course was uneventful, and the patient was discharged 14 days after she had been admitted to our hospital. Conclusions: Spontaneous hepatic rupture associated with HELLP syndrome is a very serious condition that requires prompt and decisive management. The high maternal and fetal mortality rates associated with this condition can be reduced through early accurate diagnosis and adequate management. The findings in the reported case indicate that TAE may be an attractive alternative to surgery for the management of spontaneous hepatic rupture associated with HELLP syndrome.

Diagnosis and management of pregnancies complicated by haemolysis, elevated liver enzymes and low platelets syndrome in the tertiary setting.

BACKGROUND: Haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome occurs in one to six per 1000 pregnancies; maternal death has been reported in 1-24% of cases. Vague presentation is common; hypertension and proteinuria which characterise pre eclampsia are often absent when HELLP syndrome presents. Physicians are often called on to review gravid patients with unexplained symptoms or abnormal laboratory results, and it is vital that these clinicians are aware of the myriad of ways in which HELLP syndrome may present and evolve. AIM: To describe the natural history of HELLP syndrome by providing contemporary data from our 8-year experience at The Royal Women's Hospital in Melbourne. METHODS: A retrospective analysis of the clinical and biochemical changes presentation, natural history and outcomes for 43 women whose delivery was complicated by HELLP syndrome according to Sibai criteria. RESULTS: There were two stillbirths and no neonatal or maternal deaths. Most (79%) women delivered by caesarean section. Fourteen per cent were asymptomatic at diagnosis; epigastric pain was the most common presenting symptom. Hypertension was absent at presentation for more than one-third of patients. Laboratory tests showed improvement after delivery, with platelet count showing most rapid recovery postpartum. CONCLUSION: Misdiagnosis and delayed recognition of HELLP syndrome are common due to vague and varying presentation. When HELLP syndrome is identified delivery is required to avoid catastrophic maternal and neonatal outcomes. We hope to provide guidance for general and obstetric physicians by providing contemporary evidence of the presentation and clinical course of pregnancies complicated by HELLP syndrome.

Severe HELLP syndrome masquerading as thrombocytopenic thrombotic purpura: a case report.

BACKGROUND: Thrombotic microangiopathies (TMAs) occurring in the postpartum period may be difficult to manage. They present as the combination of mechanical hemolytic anemia and consumption thrombocytopenia due to endothelial dysfunction. The cause of this endothelial aggression can be multiple: thrombocytopenic thrombotic purpura (TTP), HELLP syndrome, antiphospholipid syndrome, atypical hemolytic and uremic syndrome or acute fatty liver of pregnancy. TTP results from a severe deficiency of ADAMTS13, which is a protease cleaving specifically von Willebrand factor chiefly produced by liver cells. There are two main causes, the production of anti-ADAMTS13 auto-antibodies and, more rarely, a genetic deficiency in ADAMTS13. First-line treatment is based on plasma exchange. HELLP syndrome occurs in the third trimester of pregnancy usually in association with preeclampsia and represents a form of TMA characterized by damage to the sinusoidal capillaries of the liver. Prompt delivery is the main treatment. We present a case illustrating the challenges in discriminating between different postpartum TMAs, with a focus on the distinction between TTP and HELLP syndrome. Specifically, we highlight how acute liver failure (ALF) stemming from HELLP may lead to TTP with a spectacular response to plasma exchanges. CASE: A 28-year-old, 33 + 4 weeks pregnant woman presented with severe preeclampsia complicated by ALF in the setting of partial liver necrosis, disseminated intravascular coagulation, microangiopathic hemolytic anemia and acute kidney injury. Greatly diminished levels of ADAMTS13 (< 5%) activity and neurological impairment suggested an initial diagnosis of thrombotic thrombocytopenic purpura (TTP). Therapeutic plasma exchange (TPE) was initiated and complete renal, neurological, hematological and hepatic recovery was observed. Secondary TTP induced by ALF due to HELLP syndrome was the final diagnosis. CONCLUSION: Our case addresses the overlapping nature of postpartum TMAs and raises the possibility that HELLP-induced ALF may constitute an additional mechanism resulting in TTP, thereby opening a possible indication for TPE.

Hepatic Complications in Preeclampsia.

In cases of preeclampsia with severe features and hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome, hepatic complications portend significant short-term and long-term maternal health implications. In this section, we will discuss the physiology of normal hepatic function in pregnancy, the pathophysiology of the abnormalities noted in hepatic function during the process of preeclampsia development, the diagnosis and management of preeclampsia, imitators of HELLP syndrome, the utility of various biomarkers in the diagnosis and prognosis of the preeclampsia disease spectrum, possible underlying genetic factors predisposing women to developing hepatic abnormalities with preeclampsia, and finally prognosis and management of a subcapsular hematoma.

Liver disease in pregnancy: Medical aspects and their implications for mother and child.

Liver disease during pregnancy is more common than expected and may require specialized intervention. It is important to determine if changes in liver physiology may develop into liver disease, to assure early diagnosis. For adequate surveillance of mother-fetus health outcome, liver disease during pregnancy might require intervention from a hepatologist. Liver diseases have a prevalence of at least 3% of all pregnancies in developed countries, and they are classified into two main categories: related to pregnancy; and those non- related that are present de novo or are preexisting chronic liver diseases. In this review we describe and discuss the main characteristics of those liver diseases associated with pregnancy and only some frequent pre-existing and co-incidental in pregnancy are considered. In addition to the literature review, we compiled the data of liver disease occurring during pregnancies attended at the National Institute of Perinatology in Mexico City in a three-year period. In our tertiary referral women hospital, liver disease was present in 11.24 % of all pregnancies. Associated liver disease was found in 10.8% of all pregnancies, mainly those related to pre-eclampsia (9.9% of pregnancies). Only 0.56% was due to liver disease that was co-incidental or preexisting; the acute or chronic hepatitis C virus was the most frequent in this group (0.12%). When managing pregnancy in referral hospitals in Latin America, it is important to discard liver alterations early for adequate follow up of the disease and to prevent adverse consequences for the mother and child.

Intracerebral Hemorrhage in Women: A Review with Special Attention to Pregnancy and the Post-Partum Period.

Non-traumatic intracranial hemorrhage includes subarachnoid hemorrhage, subdural hemorrhage, and intracerebral hemorrhage (ICH), which can be classified as primary or secondary. Primary ICH is due to arterial hypertension or cerebral amyloid angiopathy, and secondary ICH is due to cerebral vascular malformations, coagulopathies, infectious complications, brain tumors, and illicit stimulant drug use. This review explores the epidemiology and management of non-traumatic ICH in women, with a focus on pregnancy and the post-partum period, defined as 6 weeks post-delivery.

The Complement Alternative Pathway and Preeclampsia.

PURPOSE OF REVIEW: Significant and intricate immune adaptations are essential for the establishment and maintenance of normal pregnancy. Preeclampsia is a morbid, potentially life-threatening disease for both mother and neonate that occurs uniquely in pregnancy, at least in part, due to maternal immune maladaptation. We aim to review the literature that focuses on case reports, diagnostic approaches, and treatment strategies for disorders of the complement alternative pathway (CAP) as related to preeclampsia. RECENT FINDINGS: There is evidence of complement dysregulation in preeclampsia and HELLP syndrome, similar to that observed in a few rare types of thrombotic microangiopathies. Complement dysregulation may be identified with functional laboratory testing as well as genetic testing. Increased utilization of a standardized diagnostic approach to establish whether persistent and/or severe cases of preeclampsia and HELLP syndrome are complement-mediated may lead to development of future treatment strategies, such as complement-targeted therapy.

Microangiopathic antiphospholipid antibody-associated syndrome in a pregnant lady.

We describe a gravid 37-year-old Chinese lady with known triple positive primary antiphospholipid syndrome with previous recurrent deep vein thrombosis and early spontaneous miscarriages. She was managed with low-molecular weight heparin, aspirin, hydroxychloroquine, prednisolone and monthly intravenous immunoglobulin. She presented with recurrent per-vaginal bleeding at 22 weeks of gestation and was found to have abruptio placentae. Anti-coagulation was held off. She subsequently delivered a stillborn at 24 weeks and anti-coagulation was restarted. Day 5 post-delivery, she developed HELLP, with hemolytic anaemia (Hb 10.1 g/dL, haptoglobin <30 g/L, LDH 2206 U/L), elevated transaminases (AST 1196 U/L, ALT 1130 U/L) and thrombocytopenia (platelet 28 × 10^9/L). There were also episodes of acute severe headache and abdominal pain assessed to be secondary to microvascular ischemia as CT did not reveal any thrombosis. Her blood pressure hovered persistently above systolic 180 mmHg, and required at least three anti-hypertensives. These were coupled with a new onset proteinuria of 2 to 3 g/day. There was no evidence of disseminated intravascular coagulation. She was assessed to have microangiopathic antiphospholipid syndrome and was started on plasmapheresis. On Day 10 post-partum, the patient complained of foul-smelling vaginal discharge and was found to have retained products of conception, which was immediately evacuated. Her course was followed by poly-microbial sepsis secondary to Enterococcus fecalis, Klebsiella Pneumoniae and Escherichia coli. The patient was further treated with imipenem and she completed eight exchanges of plasmapheresis followed by five days of intravenous immunoglobulins with good clinical and biochemical improvement.

Diagnosis and Management of HELLP Syndrome Complicated by Liver Hematoma.

Subcapsular liver hematoma is a rare but potentially life-threatening complication of preeclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome. It may present with nonspecific signs and symptoms, none of which are diagnostic, and can mimic pulmonary embolism of cholecystitis. There is no consensus on the management of subcapsular liver hematoma. Unruptured liver hematoma can be conservatively managed. When rupture occurs, surgical, endovascular approaches and, rarely, liver transplantation, may be required. Actual literature is scant and retrospective in nature. Data on follow-up, time to resolution and outcome of subsequent pregnancies are very limited. We here review the diagnosis and management of liver hematoma.

Multidisciplinary Approach to Complicated Pregnancy.

A nulliparous pregnant woman in her mid-20s and in the 32nd week of gestation presented to the emergency department with severe headache and vomiting. She had an uneventful medical history; however, the physical examination upon hospital admission revealed a hypertensive emergency, papilledema, and 2+ dipstick proteinuria. Upon establishing the diagnosis of preeclampsia, aggressive therapy with corticosteroids, antihypertensive medication, and seizure prophylaxis was initiated. Hemodynamic stability was achieved within 24 hours and the patient remained in the observation unit located within the gynecology clinic. On the ninth day postadmission, however, her condition abruptly deteriorated and advanced to imminent eclampsia, accompanied by transient vision loss, altered mental status, and acute hypertensive crisis. After the patient underwent successful emergent delivery via caesarean section, a laboratory workup revealed hemolysis, elevated liver enzymes, and low platelet count, suggesting HELLP syndrome, a serious complication of eclampsia. This patient concurrently developed posterior reversible encephalopathy syndrome, which was confirmed by magnetic resonance imaging and acute respiratory distress syndrome (the latter presented with diffuse bilateral infiltrates on x-ray and developing pulmonary edema in the absence of cardiac etiology). Because of these life-threatening dynamics, the patient was transferred to the intensive care unit for further treatment. This case is a rare cascade of life-threatening complications that developed in a patient and required skillful multidisciplinary decision making and experienced management within an acute critical care setting. The final outcome of the treatment and intensive care was successful because both the patient and child survived and had no chronic or debilitating sequelae.

[HELLP syndrome requiring therapeutic plasma exchange due to progression to multiple organ dysfunction syndrome with predominant encephalopathy, respiratory and renal insufficiency]. / HELLP syndrom vyzadující plazmaferézu pro rozvoj multiorgánové dysfunkce s dominující encefalopatií, respiracní a renální insuficiencí.

OBJECTIVE: Case report of woman with twin pregnancy complicated by HELLP syndrome which progressed to multiple organ dysfunction syndrome with predominant encephalopathy, renal and respiratory insufficiency with the need to perform repeated therapeutic plasma exchange. DESIGN: Case report. SETTING: Department of gynecology and obstetrics, University Hospital in Ostrava; Departmet of hematooncology, University Hospital in Ostrava; Department of gynecology and obstetrics, Vsetín hospital; Department of hematology and transfusion, Vsetín Hospital. RESULTS: Case of 35-year-old III gravida/II para with previously normal ongoing twin bichorionic biamniotic pregnancy in week 35+0, which was admitted to secondary care delivery room for three days lasting "flu like" symptoms and the right upper quadrant pain. She was icteric, exhausted, but normotensive (120/75 mm Hg). Acute caesarean section was performed for suspected fetal hypoxia and HELLP syndrome. The laboratory exams confirmed coagulopathy and HELLP syndrome second class during the operation. Blood loss was 800 ml. Despite standard treatment of HELLP syndrome, the condition had developed to renal insufficiency, bilateral fluidothorax, alveolar pulmonary edema, encephalopathy and hypertension. In laboratory results dominates markers of coagulopathy, thrombocytopenia and microangiopathic hemolytic anemia with presence of schistocytes. Due to multiple organ dysfunction syndrome with hemolysis of unclear origin, patient was transferred to referral hospital on sixth postoperative day. Therapeutic plasma exchange (TPEX) was promptly begun. Improvement of laboratory parameters occurred already after the first TPEX and after two days there was a significant improvement of neurological status. Nine TPEX procedures were performed. The treatment was terminated after platelet count reached 100×109/l. She was discharged from hospital 21 days after delivery. After exclusion of other clinical entities, the case was closed as postpartum thrombotic microangiopathic syndrome. CONCLUSION: Postpartum thrombotic microangiopathic syndrome includes states, which resemble HELLP syndrome with their laboratory result and clinical expression, but their behavior is different - progressively worsening with signs of disseminated intravascular coagulation and complex microangiopathy with multiple organ dysfunction. It is not responding to classic treatment of HELLP syndrome. In this cases usually improvement of patients condition follow initiation of therapeutic plasma exchange.

[Hypercapnic Raised Intracerebral Pressure - Ecmo Therapy Despite Major Intracerebral Haemorrhage]. / Kasuistik: ECMO-Einsatz bei hyperkapnischer Hirndruckkrise.

We report a case of a 29-year-old primigravida asian woman with severe peripartal HELLP-syndrome. During delivery she developed coma. HELLP syndrome, complicated by severe intracerebral hemorrhage was detected. During course of therapy with drainage of intraventricular intracerebral hemorrhage, the patient developed pneumonia followed by severe acute respiratory distress syndrome (ARDS) with critically raised ICP. After 31 days of stabilization by extracorporeal membrane oxygenation (ECMO) and lung protective ventilation the patient was weaned of ECMO therapy. Following a period of 107 days including the weaning of respirator-therapy her neurologic status improved and she was able to follow commands, move upper and lower extremities on request, and recognize her relatives.