Obstetric antiphospholipid syndrome carries an increased lifetime risk for obstetric and thrombotic complications-a population-based study.

Background: Antiphospholipid syndrome (APS) can present with either a thromboembolic event (thrombotic APS, TAPS) or an obstetric complication (obstetric APS, OAPS). Data on long-term complications in the different APS phenotypes are limited. Objectives: We aimed to compare obstetric history, antiphospholipid antibody profiles, obstetric and thromboembolic complications, and pregnancy outcomes between TAPS and OAPS. Methods: This retrospective cohort study included women who delivered singleton pregnancies between 1998 and 2020. One hundred sixteen thousand four hundred nine women were included, resulting in 320,455 deliveries. Among the included patients, 71 were diagnosed with APS, 49 were classified as OAPS, and 22 as TAPS. The demographics, obstetric, neonatal, and thrombotic outcomes were compared among TAPS, OAPS, and the general obstetric population. Results: OAPS patients had an increased risk of thrombotic events compared with the general obstetric population (odds ratio [OR] 18.0; 95% CI, 8.7-37.2). In pregnancies following the diagnosis of APS, despite standard antithrombotic treatment, OAPS patients exhibited an elevated risk of placenta-related and neonatal complications compared with the general obstetric population (late fetal loss [adjusted OR {aOR}, 15.3; 95% CI, 0.5-27.5], stillbirth [aOR, 5.9; 95% CI, 2.2-15.4], placental abruption [aOR, 4.8; 95% CI, 1.5-15.3], preeclampsia [aOR, 4.4; 95% CI, 2.5-7.7], fetal growth restriction [aOR, 4.3; 95% CI, 8.5-27.5], small for gestational age neonate [aOR, 4.0; 95% CI, 2.4-6.6], and low Apgar scores [Apgar'1: aOR, 2.6; 95% CI, 1.3-10.4; Apgar'5: aOR, 3.7; 95% CI, 1.3-10.4]). TAPS patients exhibited increased risk of preeclampsia (aOR, 3.1; 95% CI, 1.2-8). Conclusion: OAPS patients exhibit a heightened risk of thrombotic events compared with the general obstetric population. Despite treatment, OAPS and TAPS still presented obstetric complications. These findings, after confirmation in prospective studies, need to be taken into consideration when planning the treatment approach for these patients.

von Willebrand factor antigen: a biomarker for severe pregnancy complications in women with hereditary thrombotic thrombocytopenic purpura?

BACKGROUND: Hereditary thrombotic thrombocytopenic purpura (hTTP) is associated with severe obstetric morbidity (SOM) during pregnancy. Treatment with fresh frozen plasma (FFP) mitigates the risk in some women, but others respond poorly and continue to suffer obstetric complications. OBJECTIVES: To determine a possible association between SOM and elevated nonpregnant von Willebrand factor (NPVWF) antigen levels in women with hTTP and whether the latter can predict the response to FFP transfusion. METHODS: This was a cohort-based study of women with hTTP due to homozygous c.3772delA mutation of ADAMTS-13 who had pregnancies both with and without FFP treatment. Occurrences of SOM were determined from medical records. Generalized estimated equation logistic regressions and receiver operating characteristic curve analysis determined the NPVWF antigen levels associated with the development of SOM. RESULTS: Fourteen women with hTTP had 71 pregnancies; of which 17 (24%) culminated in pregnancy loss and 32 (45%) were complicated by SOM. FFP transfusions were administered in 32 (45%) of the pregnancies. Treated women had decreased SOM (28% vs 72%, p < .001) and preterm thrombotic thrombocytopenic purpura exacerbations (18% vs 82%, p < .001) and higher median NPVWF antigen levels than those of women with uncomplicated pregnancies (p = .018). Among the treated women, median NPVWF antigen levels were higher in those with SOM than in those without SOM (225% vs 165%, p = .047). Logistic regression models demonstrated a significant 2-way association between elevated NPVWF antigen levels (for SOM, odds ratio, 1.08; 95% CI, 1.001-1.165; p = .046) and SOM (for elevated NPVWF antigen levels, odds ratio, 1.6; 95% CI, 1.329-1.925; p < .001). The receiver operating characteristic curve analysis demonstrated that an NPVWF antigen level of 195% had 75% sensitivity and 72% specificity for SOM. CONCLUSION: Elevated NPVWF antigen levels are associated with SOM in women with hTTP. Women with levels >195% may benefit from increased surveillance and more intensive FFP treatment during pregnancy.

Primary Central Nervous System Lymphoma: Clinical Characteristics, Treatment Options and Therapeutic Outcome in 36 Patients. A Single Center Experience.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare aggressive non-Hodgkin's lymphoma. There are limited data on the management of PCNSL outside of clinical trials. OBJECTIVES: To report experience with three main high-dose methotrexate (HDMTX)-based protocols for PCNSL treatment at one medical center. METHODS: We conducted a retrospective review of the medical records of patients diagnosed with PCNSL who were treated at Soroka Medical Center between 2007 and 2019. RESULTS: The study included 36 patients, median age 64.9 years; 33 patients received a HDMTX backbone induction therapy, 21 (58.3%) received consolidation treatment in addition. In the entire cohort, 25 patients (75.7%) achieved complete remission (CR, CRu-unconfirmed), with mean progression-free survival (PFS) 32 ± 6.9 months and median overall survival (OS) 59.6 ± 12.4 months. More aggressive regiment such as combination of rituximab, HDMTX, cytarabine and thiotepa had better responses 5 (100%) CR, but also a higher incidence of side effects such as neutropenic fever 5 (100%). In subgroup analysis by age (younger vs. older than 60 years), the PFS was 24.2 vs. 9.3 months, and OS was 64.1 vs. 19.4 months, respectively. CONCLUSIONS: A difference in CR and PFS favored a more aggressive protocol, but the toxicity of the multiagent combinations was significantly higher. The prognosis in younger was better than in older patients, with higher rates of CR, PFS, and OS, although not statistically significant. Overall treatment outcomes are encouraging; however, there is a real need for an adaptive approach for older patients and balancing among the effectiveness and side effects.

DIC in Pregnancy - Pathophysiology, Clinical Characteristics, Diagnostic Scores, and Treatments.

Obstetrical hemorrhage and especially DIC (disseminated intravascular coagulation) is a leading cause for maternal mortality across the globe, often secondary to underlying maternal and/or fetal complications including placental abruption, amniotic fluid embolism, HELLP syndrome (hemolysis, elevated liver enzymes and low platelets), retained stillbirth and acute fatty liver of pregnancy. Various obstetrical disorders can present with DIC as a complication; thus, increased awareness is key to diagnosing the condition. DIC patients can present to clinicians who may not be experienced in a variety of aspects of thrombosis and hemostasis. Hence, DIC diagnosis is often only entertained when the patient already developed uncontrollable bleeding or multi-organ failure, all of which represent unsalvageable scenarios. Beyond the clinical presentations, the main issue with DIC diagnosis is in relation to coagulation test abnormalities. It is widely believed that in DIC, patients will have prolonged prothrombin time (PT) and partial thromboplastin time (PTT), thrombocytopenia, low fibrinogen, and raised D-dimers. Diagnosis of DIC can be elusive during pregnancy and requires vigilance and knowledge of the physiologic changes during pregnancy. It can be facilitated by using a pregnancy specific DIC score including three components: 1) fibrinogen concentrations; 2) the PT difference - relating to the difference in PT result between the patient's plasma and the laboratory control; and 3) platelet count. At a cutoff of ≥26 points, the pregnancy specific DIC score has 88% sensitivity, 96% specificity, a positive likelihood ratio (LR) of 22, and a negative LR of 0.125. Management of DIC during pregnancy requires a prompt attention to the underlying condition leading to this complication, including the delivery of the patient, and correction of the hemostatic problem that can be guided by point of care testing adjusted for pregnancy.

Placental abruption as a trigger of DIC in women with HELLP syndrome: a population-based study.

BACKGROUND: Disseminated Intravascular Coagulation (DIC) is a life-threatening condition. Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) syndrome is one of the obstetrical syndromes mostly associated with DIC and thus, high rates of fatal complications. There is a lack of information regarding epidemiologic and clinical characteristics of women who developed HELLP syndrome with and without DIC. Additionally, until now, there is no adapted and widely accepted way to diagnose DIC among pregnant women presenting with HELLP syndrome, despite the evident maternal mortality linked to the disease.Objectives: (1) Address the gaps in knowledge regarding the prevalence, epidemiologic and clinical characteristics of women with HELLP syndrome who develop DIC; and (2) determine the risk factors for the development of DIC among women with HELLP syndrome. STUDY DESIGN: This was a population-based retrospective cohort study, including all women who delivered at the Soroka University Medical Center between the years 2001-2017. The study population was divided into three groups: (1) comparison group (n = 207,266 deliveries); (2) HELLP syndrome without DIC (n = 320); (3) HELLP syndrome with DIC (n = 21). The diagnosis of DIC was based on the ICD-9 code as recorded in the obstetrical database of the Soroka University Medical Center. The coding is based on the diagnosis made by the attending physician during hospitalization. RESULTS: (1) The rate of HELLP syndrome in the study population was 0.16% (341/207,607), of them 6.16% (21/341) had DIC; (2) among patients with HELLP syndrome, those with DIC had a higher median gravidity and parity; (3) a higher rate of severe maternal morbidity including blood product transfusion, placental abruption, eclampsia, acute renal failure and maternal death was observed in those who had HELLP syndrome and DIC compared to those with HELLP syndrome without DIC and the comparison group (p-value <.001 for comparison among the three groups); (4) among women with HELLP syndrome, those with DIC had a longer median PT difference, higher serum creatinine and lower AST as well as ALT median concentrations than those without DIC; (5) patients with HELLP syndrome and DIC had a higher rate of stillbirth and postpartum death than patients in the other groups (p-value <.001 for comparison among the three groups); and (6) placental abruption was an independent risk factor for the development of DIC in women with HELLP syndrome (p-value <.001). CONCLUSIONS: (1) Among women with HELLP syndrome, those who developed DIC had a higher rate of maternal and neonatal morbidity and mortality than those without DIC; and (2) placental abruption, but not abnormal liver function, was an independent risk factor for the development of DIC in women with HELLP syndrome.

Unfolding the pathophysiology of congenital thrombotic thrombocytopenic purpura in pregnancy: lessons from a cluster of familial cases.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP), a rare, potentially life-threatening thrombotic microangiopathy, manifests either as congenital TTP or acquired forms. It is caused by the absence or severe depletion of a disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13) protease, leading to the accumulation of ultra large von Willebrand factor multimers as well as extensive platelet adhesion and clumping, which can ultimately cause severe secondary end-organ damage. Pregnancy can provoke or exacerbate TTP, leading to maternal and fetal complications. OBJECTIVE: In this report, we focused on pregnancy outcomes in a recently recognized cohort of congenital TTP patients of Bedouin Arab descent in southern Israel who were all homozygous for a novel c.3772delA variant of the ADAMTS13 gene, leading to the clinical manifestations of TTP largely during pregnancy. STUDY DESIGN: All patients presented in this study belong to 2 closely related families of Arab Bedouin descent and were found to be homozygous for a novel ADAMTS13-c.3772delA variant. The cohort consisted of 19 females; 16 of them had congenital TTP and had been pregnant and were thus included. Patient data were collected from electronic medical records. RESULTS: Of note, 13 women from our cohort, who delivered 14 fetuses (owing to 1 twin pregnancy), were diagnosed with congenital TTP following complicated pregnancies, which included recurrent pregnancy loss, stillbirth, early onset preeclampsia (both mild and severe), hemolysis, elevated liver enzymes and low platelet count syndrome, intrauterine growth restriction with abnormal Doppler flow, preterm premature rupture of membranes, and a total perinatal mortality rate of 30.7% (4/13). An additional 3 women, who were diagnosed owing to complications outside of pregnancy and at older ages, experienced TTP during their pregnancies, which occurred before diagnosis. Subsequent pregnancies were treated with fresh frozen plasma leading to a 100% fetal survival rate in the pregnancies that reached fetal viability. All placentas had lesions consistent with maternal vascular underperfusion. However, the severity and frequency of these lesions were lower in the 8 placentas from pregnancies treated with fresh frozen plasma. CONCLUSION: This case series details a distinctive cohort of congenital TTP patients, all homozygous for the same, novel ADAMTS13 variant, who presented with clinical complications during pregnancy and maternal vascular lesions of underperfusion in the placenta. Our findings imply that the variant identified in the ADAMTS13 gene in our cohort may have a specific functional impact on the placenta, and that treatment with fresh frozen plasma during pregnancy ameliorates the course of the disease, leading to a milder phenotype or a normal pregnancy in the majority of cases.

External validation of the SOX-PTS score in a prospective multicenter trial of patients with proximal deep vein thrombosis.

BACKGROUND: Using data from the SOX Trial, we recently developed a clinical prediction model for occurrence of the postthrombotic syndrome (PTS) after proximal deep vein thrombosis (DVT), termed the SOX-PTS score. The score includes anatomical extent of DVT; body mass index; and baseline Villalta score. OBJECTIVE: To externally validate the SOX-PTS score. METHODS: Logistic regression analysis of data from the ATTRACT Trial that evaluated pharmacomechanical catheter directed thrombolysis in patients with proximal DVT. The primary outcome was the occurrence of PTS (defined as Villalta score ≥ 5) from 6 to 24 months after DVT. Secondary outcomes included moderate-severe PTS (Villalta scale ≥ 10) and severe PTS (Villalta scale ≥ 14). Predictive performance was assessed by discrimination and calibration. An updated score was evaluated in an exploratory analysis. RESULTS: Six hundred and ninety-one ATTRACT patients were included, of whom 328 (47%) developed PTS. The c-statistic was 0.63; 95% confidence interval (CI) 0.59-0.67 for PTS. The model's performance appeared to be better for the outcomes moderate to severe PTS and severe PTS (c-statistic 0.67; 95% CI 0.62-0.72 for moderate-severe PTS and 0.70; 0.64-0.77 for severe PTS). An updated model with age as an additional variable performed similarly to the original model. CONCLUSION: We externally validated the SOX-PTS score for estimating the risk of developing PTS, moderate to severe PTS, and severe PTS, in patients with proximal DVT. The score may be useful to predict PTS at the time of DVT diagnosis. Further external validation in different patient cohorts is required.

Modified ISTH pregnancy-specific DIC score in parturients with liver rupture: population-based case series.

OBJECTIVES: Liver rupture and hematoma are rare life-threatening complications of pregnancy. The aims of the current study are to: (1) characterize in a population-based study all cases of liver hematoma and/or rupture; and (2) validate the utility of the International Society on Thrombosis and Haemostasis (ISTH) modified pregnancy specific disseminated intravascular coagulation (DIC) score in those cases. STUDY DESIGN: A retrospective cohort study including all patients with liver subcapsular hematoma or rupture between the years 1996 and 2012 was conducted. Information on maternal characteristics, clinical presentation, diagnostic studies, therapeutic modalities, as well as maternal and fetal outcomes was collected. The pregnancy-specific modified ISTH DIC scores were calculated from admission to discharge, a score >26 is suggestive of DIC. RESULTS: Out of 175,000 births in our database, seven patients were identified with liver rupture or subcapsular hematoma, representing a prevalence of 4:100,000 deliveries. Of those, six had liver rupture and one had subcapsular liver hematoma. One patient died of hemorrhagic shock. Four patients underwent surgical liver packing and one also underwent hepatic artery ligation. Four out of seven patients were diagnosed during the immediate postpartum period with severe features of preeclampsia or with hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Modified ISTH pregnancy-specific DIC scores were calculated for five out of seven patients, and three (60%) had a score higher than 26. Patients with higher scores received more blood product transfusions, had longer hospitalizations, and their neonates had lower 1 and 5 minutes Apgar scores. CONCLUSIONS: Elevated pregnancy-specific modified ISTH DIC score (>26) in patients with liver hematoma or rupture was associated with adverse maternal and neonatal outcomes and appeared to perform well in distinguishing high and low-risk cases. Postpartum preeclampsia may be associated with severe features and a more complicated disease course.

Dabigatran-induced nephropathy and its successful treatment with Idarucizumab - case report and literature review.

BACKGROUND: Anticoagulant induced renal injury has been previously described with Warfarin treatment. In the last decade direct oral anticoagulants (DOAC) were introduced. They include direct inhibitors of factor Xa (Rivaroxaban, Apixaban, Edoxaban) and a thrombin inhibitor (Dabigatran). There are isolated reports describing acute kidney injury (AKI) due to the use of DOACs. CASE REPORT: We report a clinical case of an 80-year-old patient recently started on Dabigatran for new onset atrial fibrillation. She presented with AKI and hematuria, urine specimen showed RBC casts, and a working diagnosis of anticoagulant nephropathy due to Dabigatran was made. During hospitalization she was treated with Idarucizumab with a full recovery of renal function. To the best of our knowledge, there are 4 published case reports describing kidney injury produced by Dabigatran. CONCLUSION: The use of DOACs is increasing rapidly, with increasing concern about its safety profile and, in particular, its potential harmful effect on renal function. As described in our case, treatment with Praxbind for Dabigatran induced kidney injury may be an acceptable management strategy that may obviate the need for urgent dialysis in selected cases by complete reversal of the AKI.

How I treat the postthrombotic syndrome.

The postthrombotic syndrome (PTS) is a chronic complication of deep vein thrombosis (DVT) that imposes significant morbidity, reduces quality of life, and is costly. After DVT, 20% to 50% of patients will develop PTS, and up to 5% will develop severe PTS. The principal risk factors for PTS are anatomically extensive DVT, recurrent ipsilateral DVT, obesity, and older age. By preventing the initial DVT and DVT recurrence, primary and secondary prophylaxis of DVT will reduce occurrence of PTS. The effectiveness of elastic compression stockings (ECSs) for PTS prevention is controversial. Catheter-directed thrombolysis is not effective to prevent PTS overall but may prevent more severe forms of PTS and should be reserved for select patients with extensive thrombosis, recent symptoms onset, and low bleeding risk. For patients with established PTS, the cornerstone of management is ECS, exercise, and lifestyle modifications. Surgical or endovascular interventions may be considered in refractory cases. Because of a lack of effective therapies, new approaches to preventing and treating PTS are needed. This article uses a case-based approach to discuss risk factors for PTS after DVT, how to diagnose PTS, and available means to prevent and treat PTS, with a focus on new information in the field.

Prevention and treatment of the post-thrombotic syndrome.

Post-thrombotic syndrome (PTS) is a complication that develops in up to 50% of patients with deep vein thrombosis (DVT) and manifests as symptoms and signs of chronic venous insufficiency of varying severity. PTS negatively affects patient's quality of life and causes significant burden to the healthcare system. The risk for PTS development can be markedly reduced by preventing DVT and providing appropriate anticoagulation once it develops. Patients with extensive proximal (iliofemoral) DVT may benefit from invasive interventions, such as catheter-directed thrombolysis. The effectiveness of elastic compression stockings (ECS) for PTS prevention has not been conclusively demonstrated in randomized trials. Treatment of PTS is primarily based on ECS, exercise and lifestyle modifications. The effectiveness of various pharmacologic agents for PTS treatment remains controversial. Surgical or radiological interventions for vein reconstruction or revascularization may be considered in refractory cases. This review summarizes current evidence regarding prevention and treatment of PTS of the lower limbs in adults.

LMWH in the prevention of preeclampsia and fetal growth restriction in women without thrombophilia. A systematic review and meta-analysis.

Placental mediated pregnancy complications such as preeclampsia and fetal growth restriction (FGR) are common, serious, and associated with increased morbidity and mortality. We conducted a systematic review and meta-analysis to determine the effect of treatment with low-molecular-weight heparins (LMWHs) for secondary prevention of these complications in non thrombophilic women. We searched the electronic databases PubMed, Scopus, and Cochrane Library for randomised controlled trials addressing this question. Five studies including 403 patients met the inclusion criteria, 68 developed preeclampsia and 118 FGR. The studies were very heterogeneous in terms of inclusion criteria, LMWH preparation, and dosage. Meta-analyses were performed using random-effect models. The overall use of LMWHs was associated with a risk reduction for preeclampsia (Relative risk (RR) 0.366; 95 % confidence interval (CI), 0.219-0.614) and FGR (RR 0.409; 95 % CI, 0.195-0.932) vs. no treatment. From the data available for analysis it appears that the use of Dalteparin is associated with a risk reduction for preeclampsia (p=0.002) and FGR (p<0.001); while Enoxaparin is associated with risk reduction for preeclampsia (p=0.013) but not for FGR (p=0.3). In spite of the small number of studies addressing the research question, and the high variability among them, our meta-analysis found a modest beneficial effect of LMWH for secondary prevention of preeclampsia and FGR. Further studies are needed to address these questions before a definite conclusion can be reached.

Association between inflammation biomarkers, anatomic extent of deep venous thrombosis, and venous symptoms after deep venous thrombosis.

OBJECTIVE: Inflammation may play a role in pathogenesis of venous thromboembolism, but the nature of this relationship is not yet understood. The objective of this study was to assess whether inflammation marker levels measured at diagnosis of deep venous thrombosis (DVT) and change in levels during the first month after DVT are associated with anatomic extent of DVT and severity of venous signs and symptoms at baseline and 1 month. METHODS: The BioSOX study is a biomarker substudy of the Compression Stockings to Prevent the Post-Thrombotic Syndrome (SOX) trial, a multicenter, randomized controlled trial that included patients with a first, acute, symptomatic, proximal DVT. Blood samples were collected from participants at baseline and 1 month, and C-reactive protein (CRP), intercellular adhesion molecule 1, interleukin (IL)-6, and IL-10 were measured by established assays. Linear regression was used to assess the association between continuous log-transformed baseline biomarker levels and anatomic extent of DVT, classified as iliac or common femoral DVT vs femoral or popliteal DVT (reference). Proportional odds ordinal logistic regression models were used to analyze the association between biomarker level and Villalta score (as a measure of severity of venous signs and symptoms) at baseline and 1 month. RESULTS: Among 717 patients, 60.2% were male, and the mean age was 55.2 years. There was a significant association between more extensive DVT (common femoral or iliac) and levels of CRP and IL-6 at DVT diagnosis. Median (interquartile range) CRP level was 11.6 mg/L (3.84-39.5) in patients with common femoral or iliac DVT vs 6.86 mg/L (3.11-22) in patients with popliteal or femoral DVT, and median IL-6 level was 6.36 pg/mL (1.09-14.37) vs 4.40 pg/mL (2.35-8.27), respectively. These differences were statistically significant in linear regression analyses. In addition, compared with those in the lowest quartile, each higher quartile of baseline CRP concentration was associated with an odds ratio of 2.89 (1.93-4.33) for having a more severe Villalta category at baseline and 1.98 (1.28-3.08) for having a more severe Villalta category 1 month after DVT. Higher baseline levels of IL-6 were associated with Villalta severity category at baseline (odds ratio, 2.40 [1.61-3.59]). Change in biomarker levels during the first month after DVT was not strongly associated with the 1-month Villalta score. CONCLUSIONS: Levels of CRP and IL-6 at DVT diagnosis were associated with thrombotic disease burden, as measured by DVT extent, and severity of DVT symptoms and signs. Further studies are required to more fully elucidate the role of inflammation in DVT and its clinical course.

How to predict and diagnose postthrombotic syndrome.

Postthrombotic syndrome (PTS) is the most frequent complication of deep vein thrombosis (DVT). From 20% to 50% of the patients will develop PTS after DVT, and from 5% to 10%, severe PTS. PTS is diagnosed on clinical grounds, based on the presence of signs and symptoms of venous insufficiency in the leg ipsilateral to DVT. The Villalta scale, a clinical scale that incorporates venous symptoms and signs, is a recommended standard for the diagnosis of PTS. Identifying which patients are at high risk of developing PTS would help improve the management of patients with DVT and allow physicians to provide patients with individualized information on their expected prognosis. Clinical predictors of PTS have been progressively characterized, but the ability to predict which patient with DVT is likely to develop PTS remains limited. A number of risk factors for PTS have been identified; of these, proximal location of DVT and a previous ipsilateral DVT are the most important. This review discusses the knowledge gained over the last decade on the diagnosis and predictors of PTS.  

The predictive value of markers of fibrinolysis and endothelial dysfunction in the post thrombotic syndrome. A systematic review.

The post thrombotic syndrome (PTS) develops in 20-40% of deep venous thrombosis (DVT) patients. Risk factors for PTS have not been well elucidated. Identification of risk factors would facilitate individualised risk assessment for PTS. We conducted a systematic review to determine whether biomarkers of fibrinolysis or endothelial dysfunction can predict the risk for PTS among DVT patients. Studies were identified by searching the electronic databases PubMed, EMBASE, Scopus and Web of science. We included studies published between 1990 and 2013, measured biomarker levels in adult DVT patients, and reported rates of PTS development. Fourteen studies were included: 11 investigated the association between D-dimer and PTS; three examined fibrinogen; two measured von Willebrand factor; one measured plasminogen activator inhibitor-1; one assessed ADAMTS-13 (A Disintegrin and Metalloprotease with Thrombospondin type 1 repeats) and one measured factor XIII activity. Studies varied with regards to inclusion criteria, definition of PTS, time point and method of biomarker measurement. We were unable to meta-analyse results due to marked clinical heterogeneity. Descriptively, a significant association with PTS was found for D-dimer in four studies and factor XIII in one study. Further prospective research is needed to elucidate whether these markers might be useful to predict PTS development.

Association between Thrombophilia and the Post-Thrombotic Syndrome.

The post thrombotic syndrome (PTS) is a chronic condition that develops in 20%-40% of deep vein thrombosis (DVT) patients. While risk factors that predispose to the development of venous thromboembolism (VTE) are widely known, factors that influence the development of PTS after DVT have not been well elucidated. Over 10% of the general population is affected by one or more identifiable inherited thrombophilias which have been shown to underlie at least 1/3 of cases of VTE. The various thrombophilias are important risk factors for VTE, but it is unknown whether they also increase the risk for development of PTS. We performed a review of studies that have reported on the association between thrombophilia and the development of PTS in populations of patients with DVT and with chronic venous ulcers. Studies vary with regards to the definition of PTS, study design, follow-up period, and present conflicting results. Based on these results, the question of whether thrombophilia predisposes to the development of PTS remains unanswered.