The structure of the von Willebrand factor is not altered in patients with colorectal carcinoma

Aim Elevated levels of von Willebrand factor (VWF) are often observed in many diseases including colorectal cancer, but this finding is not definite. The aim of our study was to examine the change in VWF multimer distribution in patients with colorectal cancer. Method We randomly selected nine patients from each of the four Union for International Cancer Control (UICC) stages of colon cancer. VWF antigen (VWF:Ag), VWF‐cleaving protease ADAMTS‐13 level and factor VIII activity (FVIII:C) were determined. The multimer distribution of VWF was visualized using electrophoretic multimer analysis. Results The VWF multimer structure was normal with no difference between the four UICC stages. There was no significant increase in VWF:Ag and FVIII:C levels in the more advanced UICC stages. There was no significant difference in the ADAMTS‐13 level according to the UICC stage. Conclusion There was no change in the VWF multimer distribution to indicate acquired von Willebrand disease.     

Subarachnoid hemorrhage associated with von Willebrand's disease--case report

A 59-year-old woman with type IIA von Willebrand's disease (VWD) presented with subarachnoid hemorrhage (SAH). Computed tomography showed SAH in the right sylvian fissure and intracranial hemorrhage in the right temporal lobe. Angiography demonstrated an aneurysm at the bifurcation of the right middle cerebral artery. Neck clipping was performed on the 3rd day after the onset with intra- and postoperative administration of factor VIII/von Willebrand factor concentrate. No excessive bleeding occurred. Patients with prolonged bleeding time should be screened for VWD before surgery. This is a rare case of VWD presenting with SAH secondary to ruptured intracranial aneurysm. The clinical characteristics and the management of SAH in a patient with VWD are discussed.     

Non-surgical bleeding in patients with ventricular assist devices could be explained by acquired von Willebrand disease.

OBJECTIVE: Outcomes after ventricular assist device (VAD) implantation have significantly improved during the last decade. However, bleeding episodes remain a serious complication of VAD support. This cannot be explained by the individual anticoagulation regimen alone in several cases, but may be symptomatic of acquired von Willebrand disease (VWD). The leading finding in acquired VWD (AVWD) is the loss of large multimers which results in diminished binding to collagen and to the platelets. We, therefore, analysed patients with two VAD types for laboratory parameters of VWD and compared them with patients after heart transplantation (HTX). MATERIALS AND METHODS: Seven patients with a HeartMate II left-ventricular assist device and five patients who received a Thoratec biventricular assist device were included in this study. Eight HTX recipients served as controls. Analysis included international normalized ratio (INR), partial thromboplastin time (PTT), platelet count, von Willebrand factor (VWF) antigen, collagen binding capacity, ristocetin cofactor activity, the ratios of the latter two to the VWF antigen and presence of large VWF multimers. RESULTS: The VAD and HTX groups did not differ with regard to age or time-point of analysis after surgery. INR and number of platelets were comparable in both groups, PTT was prolonged in VAD patients. Both VAD and HTX patients had elevated but comparable amounts of VWF antigen. However, large multimers were missing in all of 10 tested VAD patients. In contrast, five of six tested HTX recipients displayed normal multimer pattern. Indeed, collagen binding capacity and ristocetin cofactor activity (which measures binding of VWF to platelets) were lower in VAD patients compared to HTX recipients. Impaired coagulation associated with VADs was also reflected by the diminished ratios of collagen binding capacity and ristocetin cofactor activity to VWF antigen. A pathologic collagen binding ratio was found in all 10 tested VAD patients and one of the eight HTX patients, a reduced ristocetin cofactor activity ratio in 10 of 12 VAD and one of eight HTX patients. CONCLUSION: Non-surgical postoperative bleeding after VAD implantation could be explained by an AVWD. Several pharmacologic treatment options (tranexamic acid, desmopressin, VWF-factor VIII concentrate, recombinant factor VIIa) may arise from our data. Improved VAD design could prevent this problem in the future.     

Impact of high mechanical shear stress and oxygenator membrane surface on blood damage relevant to thrombosis and bleeding in a pediatric ECMO circuit

The roles of the large membrane surface of the oxygenator and the high mechanical shear stress (HMSS) of the pump in the extracorporeal membrane oxygenation (ECMO) circuit were examined under a pediatric support setting. A clinical centrifugal pump and a pediatric oxygenator were used to construct the ECMO circuit. An identical circuit without the oxygenator was constructed for comparison. Fresh human blood was circulated in the two circuits for 4 hours under the identical pump speed and flow. Blood samples were collected hourly for blood damage assessment, including platelet activation, generation of platelet-derived microparticles (PDMP), losses of key platelet hemostasis receptors (glycoprotein (GP) Ibα (GPIbα) and GPVI), and high molecular weight multimers (HMWM) of von Willebrand factor (VWF) and plasma free hemoglobin (PFH). Platelet adhesion on fibrinogen, VWF, and collagen was further examined. The levels of platelet activation and generation of PDMP and PFH exhibited an increasing trend with circulation time while the expression levels of GPIbα and GPVI receptors on the platelet surface decreased. Correspondingly, the platelets in the blood samples exhibited increased adhesion capacity to fibrinogen and decreased adhesion capacities on VWF and collagen with circulation time. Loss of HMWM of VWF occurred in both circuits. No statistically significant differences were found in all the measured parameters for blood damage and platelet adhesion function between the two circuits. The results indicate that HMSS from the pump played a dominant role in blood damage associated with ECMO and the impact of the large surface of the oxygenator on blood damage was insignificant.     

Development of a Severe von Willebrand Factor/ADAMTS13 Dysbalance During Orthotopic Liver Transplantation

Patients with liver disease show profound changes in their hemostatic system, which may further change during liver transplantation. We previously demonstrated that highly elevated levels of the platelet adhesive protein von Willebrand factor (VWF) in patients with cirrhosis lead to an increased VWF-dependent platelet deposition under flow as compared to healthy controls. In this study we examined VWF parameters during the course of liver transplantation. We collected serial plasma samples from 20 patients undergoing liver transplantation in which we determined plasma levels of VWF and the VWF-cleaving protease ADAMTS13. Furthermore, we performed functional tests of VWF-dependent platelet adhesion. We found persistently elevated levels of VWF during and after liver transplantation. The capacity of VWF to interact with platelets normalized during the course of transplantation, and flow-mediated VWF-dependent platelet adhesion remained at levels far exceeding those observed in healthy individuals during and after transplantation. Plasma levels of ADAMTS13 dropped during transplantation, and in four patients levels below 10% of normal were observed after reperfusion. We observed the development of a hyperreactive primary hemostatic system, as evidenced by high levels of fully functional VWF and a temporary ADAMTS13 deficiency, during liver transplantation, and speculate that these changes contribute to postoperative thrombotic complications.     

Peripartum management of a parturient with type 1C (clearance) von Willebrand disease

Peripartum replacement of factor VIII and von Willebrand factor is not usually required in type 1 von Willebrand disease, as the levels of endogenous factors tend to increase to within the normal range as a physiological change of pregnancy. However, there is wide heterogeneity of genotypes and phenotypes associated with type 1 von Willebrand disease. Here, we describe the anesthetic management of a parturient with type 1C von Willebrand disease, a subtype characterized by decreased plasma von Willebrand factor survival.     

Successful management of severe refractory acquired immune bleeding disorder: Prior to insisting surgery

INTRODUCTION

Acquired bleeding disorders are rare and may be missed before surgery. Additionally, they may be refractory to conventional treatments.

PRESENTATION OF CASE

A 50-year-old patient experienced prolonged post-operative bleeding when his bleeding disorder was missed prior to his undergoing inguinal herniorrhaphy. Post-operative investigations revealed severe acquired von Willebrand syndrome associated with a monoclonal gammopathy of undetermined significance. A few months later, he required umbilical herniorrhaphy, but he did not respond to attempts to raise his von Willebrand factor antigen and activity levels using conventional therapies, including desmopressin, cryoprecipitate, intravenous immunoglobulin, and Von Willebrand factor concentrate. A triple therapy combination of dexamethasone, intravenous immunoglobulin, and mycophenolate mofetil was administered, with a successful and sustained response, lasting about 2 months. The surgery was performed safely, without any complications.

DISCUSSION

Conventional acquired von Willebrand syndrome treatment is usually aimed at replacing von Willebrand factor or stimulating its secretion from storage in endothelial cells. In the present case, the alternative treatment was directed against both the humoral and cell-mediated immune mechanisms.

CONCLUSION

This case of acquired bleeding disorder showed that more attention must be given to a patient''s coagulation profile, even if only very minor laboratory coagulation derangements are detected prior to surgery, to avoid missing such rare disorders. The described triple therapy demonstrated good effects and may be considered for inclusion in a controlled randomized study to determine its usefulness for other surgeries delayed due to severe acquired bleeding disorders. To the best of our knowledge, this triple combination treatment has not been previously used for the treatment of severe acquired bleeding disorders that are refractory to conventional therapies.Abbreviations: APTT, activated partial thromboplastin time; VWF Ag, von Willebrand factor antigen; VWF Act, von Willebrand factor activity; IgG, immunoglobulin G; aVWS, acquired von Willebrand syndrome; VWF, von Willebrand factor; MGUS, monoclonal gammopathy of undetermined significance; MMF, mycophenolate mofetil; DIM, dexamethasone, intravenous immunoglobulin, mycophenolate mofetil; VWD, von Willebrand disease     

Acute rejection before cytomegalovirus infection enhances von Willebrand factor and soluble VCAM-1 in blood

BACKGROUND: Human cytomegalovirus (HCMV) infections in transplantation patients are associated with vascular endothelial damage. This is reflected by the appearance of cytomegalic endothelial cells (CECs) and noninfected endothelial cells (ECs) in blood. To get more insight in the extent of vascular damage during HCMV infection, we investigated the levels of soluble markers during HCMV infection in relationship to EC levels and also preceding the acute rejection episodes. METHODS: Of 46 kidney transplant patients, plasma levels of von Willebrand factor (VWF), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble E-selectin (sE-sel) were analyzed during the course of HCMV infection. RESULTS: Plasma levels of VWF and sVCAM-1 increased twofold during severe HCMV infection. Moreover, the plasma levels of VWF correlated with detectable cytomegalic and noninfected ECs in blood. The kinetics of changes in VWF and ECs (CEC and EC) demonstrated the relationship with HCMV-induced vascular damage. Levels of sICAM-1 and sE-sel in plasma did not significantly change during HCMV infection. Interestingly, the combination of HCMV infection and preceding acute transplant rejection caused the highest increases of VWF and sVCAM-1 plasma levels, reflecting an enhanced susceptibility for endothelial damage at the moment of infection. CONCLUSION: CMV infection is associated with vascular damage, and the vascular damage during CMV infection is enhanced if patients experienced acute rejection before CMV infection.     

Severe upper gastrointestinal bleeding in Heartmate II induced by acquired von Willebrand deficiency: anticoagulation management

Patients treated with continuous flow assist devices may have increased bleeding tendencies due to an induced high molecular weight von Willebrand factor (VWF) multimer deficiency. We report a patient supported with a HeartMate II (Thoratec, Pleasanton, CA) who developed severe gastrointestinal bleeding refractory to conventional therapy and needing a total of 60 transfusions. After documenting the lack of large VWF multimers, suggestive of a defective platelet function, the patient was switched from aspirin to warfarin therapy (target international normalized ratio between 1.5 and 2.0). Three days after changing the anticoagulant regimen, the patient stopped bleeding and required no further transfusion.     

Device‐induced platelet dysfunction in mechanically assisted circulation increases the risks of thrombosis and bleeding

Thrombotic and bleeding complications are the major obstacles for expanding mechanical circulatory support (MCS) beyond the current use. While providing the needed hemodynamic support, those devices can induce damage to blood, particularly to platelets. In this study, we investigated device‐induced alteration of three major platelet surface receptors, von Willebrand factor (VWF) and associated hemostatic functions relevant to thrombosis and bleeding. Fresh human whole blood was circulated in an extracorporeal circuit with a clinical rotary blood pump (CentriMag, Abbott, Chicago, IL, USA) under the clinically relevant operating condition for 4 hours. Blood samples were examined every hour for glycoprotein (GP) IIb/IIIa activation and receptor loss of GPVI and GPIbα on the platelet surface with flow cytometry. Soluble P‐selectin in hourly collected blood samples was measured by enzyme linked immunosorbent assay to characterize platelet activation. Adhesion of device‐injured platelets to fibrinogen, collagen, and VWF was quantified with fluorescent microscopy. Device‐induced damage to VWF was characterized with western blotting. The CentriMag blood pump induced progressive platelet activation with blood circulating time. Particularly, GPIIb/IIIa activation increased from 1.1% (Base) to 11% (4 hours) and soluble P‐selectin concentration increased from 14.1 ng/mL (Base) to 26.5 ng/mL (4 hours). Those device‐activated platelets exhibited increased adhesion capacity to fibrinogen. Concurrently, the CentriMag blood pump caused progressive platelet receptor loss (GPVI and GPIbα) with blood circulating time. Specifically, MFI of the GPVI and GPIbα receptors decreased by 17.2% and 16.1% for the 4‐hours sample compared to the baseline samples, respectively. The device‐injured platelets exhibited reduced adhesion capacities to collagen and VWF. The high molecular weight multimers (HMWM) of VWF in the blood disappeared within the first hour of the circulation. Thereafter the multimeric patterns of VWF were stable. The change in the VWF multimeric pattern was different from the progressive structural and functional changes of platelets with the circulation time. This study suggested that the CentriMag blood pump could induce two opposite effects on platelets and associated hemostatic functions under a clinically relevant operating condition. The device‐altered hemostatic function may contribute to thrombosis and bleeding simultaneously as occurring in patients supported by a rotary blood pump. Device‐induced damage of platelets may be an important cause for bleeding in patients supported with rotary blood pump MCS systems relative to device‐induced loss of HMWM‐VWF.     

Von Willebrand factor (VIII R:Ag), fibronectin, and insulin-like growth factors I and II in diabetic retinopathy and nephropathy

We have measured plasma von Willebrand factor (VWF) as the factor VIII-related antigen, plasma fibronectin, and two of the serum somatomedins, insulin-like growth factor I (IGF I) and IGF II, in 51 diabetic patients and 25 nondiabetic control subjects. VWF was significantly higher in the diabetic group than in the controls (173 +/- 9% SEM versus 101 +/- 9%, P less than 0.001), as has been reported by others. However, within the diabetic group there was no significant difference in VWF between those patients without retinopathy, those with background or proliferative retinopathy, or those with macular edema. There was also no difference in VWF between the diabetic subjects with and those without proteinuria. These results rule against a previously advanced hypothesis that the increase in VWF in patients with diabetes is secondary to microangiopathy. No significant difference was observed in fibronectin, IGF I, or IGF II between the diabetic and control groups, between the diabetic group without retinopathy and the retinopathic subgroups, and between the diabetic subjects with and without proteinuria. In the diabetic patients, there was no correlation between diabetic control as assessed by glycosylated hemoglobin and glycosylated serum protein, and the plasma levels of VWF, fibronectin, IGF I, or IGF II. The results of this study strongly suggest that neither plasma VWF, fibronectin, IGF I, nor IGF II plays an important primary role in the pathogenesis of diabetic microvascular disease, although one or more of these factors might play a permissive role.     

Molecular basis of ADAMTS13 dysfunction in thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathic disorder characterized by thrombocytopenia, hemolytic anemia, neurological and renal manifestations, and fever. It is associated with dysfunctional von Willebrand factor (VWF) proteolysis and the occurrence of VWF- and platelet-rich thrombi in the microcirculation of multiple organs, including the kidneys. Von Willebrand factor is a large glycoprotein that circulates in plasma as a series of multimers, and it plays a major role in primary hemostasis by inducing the formation of platelet plugs at sites of vascular injury and high-shear stress. Its activity is dependent on the sizes of the multimers, with ultra-large (UL) VWF multimers being biologically very potent. The ULVWF multimers are rapidly degraded upon their secretion from endothelial cells in normal individuals but not in the circulation of TTP patients, causing the formation of disseminated thrombi in the latter. The defective breakdown of VWF is attributed to a severely deficient activity of the VWF-cleaving protease ADAMTS13, a plasma metalloprotease synthesized in the liver, kidneys, and endothelium. This protease rapidly degrades VWF-platelet strings under flow by proteolytic cleavage of the VWF subunit, thereby regulating the size of the platelet thrombus. Congenital TTP occurs due to ADAMTS13 mutations, with the usual debut occurring during the first years of life, while acquired TTP is associated with auto-antibodies against ADAMTS13.     

Does desmopressin acetate prophylaxis reduce blood loss after valvular heart operations? A randomized, double-blind study.

The effectiveness of prophylactic desmopressin acetate in reducing hemorrhage after cardiopulmonary bypass operations is controversial. We conducted a prospective, randomized, placebo-controlled, double-blind trial to determine its effectiveness and safety in such patients. Eighty-three evaluable patients undergoing valvular heart operations were randomized to receive desmopressin (0.3 microgram/kg) (41) or placebo (42) after cardiac bypass. Demographic characteristics were similar in both groups. There was no significant difference in total 24-hour blood loss between groups (desmopressin 1064.8 +/- 647.1 ml versus placebo 844.4 +/- 507.6 ml; p greater than 0.05), or in the requirement for red blood cell, platelet, or fresh frozen plasma transfusion, or for reexploration for control of hemorrhage. Neither was there a difference in the occurrence of thrombotic complications between groups. Analysis of factor VIII activity, von Willebrand factor, or von Willebrand factor multimers failed to show significant correlations with blood loss or differences between groups except for factor VIII activity, which was significantly higher in the desmopressin group 1 hour after operation than in the placebo group. A detailed comparative analysis of similar trials to determine the reasons for different outcomes suggests that desmopressin should not be used routinely as a prophylactic agent to reduce postsurgical hemorrhage, but that it may be beneficial when used in patients who already manifest excessive bleeding postoperatively.     

Vascular proliferation in the stroma of gastric cancer and its significance]

To elucidate vascular characteristics in the stroma of gastric cancer, the morphological and immunohistochemical changes of vascular components were examined in 27 gastric cancers and 7 noncancer gastric tissues including 2 peptic ulcers. In differentiated adenocarcinoma, a large number of blood vessels were observed in vicinity of the cancer glands and type IV collagen (C-IV) was localized around the blood vessels and cancer glands, and ultrastructurally, cytoplasmic organelle and weibel-Palade bodies were encountered in the endothelium. In poorly differentiated adenocarcinoma, a small number of blood vessels were distributed sporadically in the stroma and there were vascular endothelia in which von Willebrand factor (VWF) was localized, and there were much more endothelia in which VWF was not localized compared with differentiated adenocarcinoma. C-IV was localized only around the blood vessels and OKM5 was localized in the endothelia which were distributed in the center of cancer nest in poorly differentiated adenocarcinoma. Ultrastructurally, there were not so many Weibel-Palade bodies in the endothelia without complete basement membrane. The morphological and functional changes of blood vessels were correlated with cancer differentiation and metastasis. These changes may provide biological feature of cancer and may be induced by cancer cells, vascular endothelia and mesenchymal cells.     

Acquired von Willebrand syndrome after exchange of the HeartMate XVE to the HeartMate II ventricular assist device

Instead of pulsatile ventricular assist devices an increasing number of nonpulsatile ventricular assist devices are introduced to clinical practice. The different flow characteristics of this new technique lead to alteration in shear stress on blood components, which may affect the coagulation system. Repeated von Willebrand factor analyses were performed in a patient who first was implanted with a pulsatile ventricular assist device (Thoratec HeartMate XVE), which had to be replaced after 405 days with an axial flow device (HeartMate II). During support with the pulsatile ventricular assist device there was no sign of any coagulation disorder. However, on the axial flow device acquired von Willebrand syndrome Type 2 developed. Inhibition of platelet function was also observed, which may be in part due to the von Willebrand syndrome. The HeartMate II axial flow device may induce von Willebrand syndrome, which was not observed in HeartMate XVE pulsatile ventricular assist device. Patients put on continuous flow devices should be screened for acquired von Willebrand syndrome.     

The reinnervation pattern of wounds and scars may explain their sensory symptoms.

Anaesthesia, pruritis and pain are common in cutaneous scars. The reinnervation pattern of healing wounds and scars might help to explain these symptoms, as sensory neurotransmitters are known to be mediators of inflammation and healing. We quantified the regeneration patterns of blood vessels and nerves in excisional skin wounds as they matured into scars. Mice underwent 1cm(2) full thickness skin excisions. Wounds were harvested between five and 84 days. Sections underwent immunohistochemical staining for protein gene product 9.5 (PGP9.5) a pan-neuronal marker, and the sensory neuropeptides calcitonin gene related peptide (CGRP) and substance P (SP). The endothelial marker von Willebrand factor (VWF) was used to allow co-localisation and quantification of blood vessels. Nerve fibre density was quantified at multiple sites within wounds. There was no difference in the reinnervation/revascularisation pattern between peripheral and central sites. The density of PGP9.5, CGRP, SP and VWF peaked between 14 and 42 days, and levels of PGP9.5, CGRP and VWF all decreased to approximately those found in unwounded skin by 84 days (mature scar). SP levels, however, remained elevated at approximately twice the density found in unwounded skin. Increased densities of SP and CGRP in healing wounds could explain the unpleasant sensory symptoms of healing wounds.     

Analgésie péridurale obstétricale et maladie de Willebrand de type 2B

Type 2B von Willebrand disease (vWD) is an inherited bleeding syndrome resulting from a qualitative abnormality of von Willebrand Factor with an increased affinity for the glycoprotein Ib platelet receptor. Pregnancy increases the severity of this disease by decreasing the platelet count restricting epidural anaesthesia because of adverse risk of spinal bleeding. There is a phenotypic variability of Type 2B vWD depending of the von Willebrand Factor mutation. We report here the strategy we used to administer epidural anaesthesia for a patient with Type 2B vWD resulting from the P1337L mutation of von Willebrand Factor.     

Plasma von Willebrand factor levels correlate with clinical outcome of severe traumatic brain injury

Biochemical markers of cellular stress/injury have been proposed to indicate outcome after head injury. The aim of the present study was to determine whether plasma von Willebrand factor (VWF) levels correlate with primary outcome and with clinical variables in severe traumatic brain injury (TBI). Forty-four male patients, victims of severe TBI, were analyzed. Clinical outcome variables of severe TBI comprised survival and neurological assessment using the Glasgow Outcome Scale (GOS) at intensive care unit (ICU) discharge. Computerized tomography (CT) scans were analyzed according to Marshall CT classification. Three consecutive venous blood samples were taken: first sample (11.4 +/- 5.2 h after trauma, mean +/- SD), and 24 h and 7 days later. The result of mean plasma VWF concentration was significantly higher in the TBI group (273 U/dL) than in the control group (107 U/dL; p < 0.001). Severe TBI was associated with a 50% mortality rate. Nonsurvivors presented significantly higher APACHE II scores than survivors (nonsurvivors mean, 18.8; survivors mean, 12.7; p < 0.001), and also presented higher scores in Marshall CT classification (nonsurvivors mean, 4.6; survivors mean, 2.7; p < 0.05). There was a significant positive correlation between plasma levels at second plasma sampling and scores in Marshall CT classification (p < 0.05). The sensitivity of plasma VWF concentration in predicting mortality according to the cut-off of 234 U/dL was 64%, with a specificity of 68%. Therefore, VWF increases following severe TBI may be a marker of unfavorable outcome.     

Development of a Hyperactive Primary Hemostatic System During Off‐Pump Lung Transplantation Resulting From an Unbalance Between von Willebrand Factor and Its Cleaving Protease ADAMTS13

An unbalance between the platelet‐adhesive protein von Willebrand factor (VWF) and its cleaving protease ADAMTS13 is a risk factor for thrombosis. Here, we assessed levels and functionality of VWF and ADAMTS13 in patients undergoing off‐pump lung transplantation. We analyzed plasma of 10 patients and distinguished lung transplantation‐specific effects from those generally accompanying open‐chest surgeries by comparing results with 11 patients undergoing off‐pump coronary bypass graft (CABG) surgery. Forty healthy volunteers were included for reference values. VWF antigen levels as well as the VWF ristocetin cofactor activity/VWF antigen ratio increased during lung transplantation and after CABG surgery. An increase in VWF propeptide levels was paralleled by a decrease in ADAMTS13 activity. This was more pronounced during lung transplantation. Similarly, the capacity of plasma to support platelet aggregation under shear flow conditions in vitro was more increased during lung transplantation. The proportion of high molecular weight VWF multimers was elevated in both groups without evidence for ultra‐large VWF. VWF's collagen binding activity remained unchanged. In conclusion, a hyperactive primary hemostatic system develops during lung transplantation resulting both from a pronounced (functional) increase of the VWF molecule and decrease of ADAMTS13. This may increase the risk of platelet thrombosis within the allograft.     

Thrombocytopenia during pregnancy: from etiologic diagnosis to therapeutic management

Thrombocytopenia complicates 10% of all pregnancies. It has many potential causes, but three are responsible for almost all cases: incidental gestational thrombocytopenia (IGT) (74%), preeclampsia and HELLP (hemolysis, elevated liver function tests, low platelet count) syndrome (21%) and immune thrombocytopenic purpura (ITP) (4%). Although there is no risk of maternal or fetal hemorrhage with IGT, a benign disorder, preeclampsia, HELLP syndrome and ITP expose mother and child to potentially life-threatening complications. Other rare causes are also associated with severe complications: thrombotic thrombocytopenic purpura, hemolytic and uremic syndrome, disseminated intravascular coagulation and von Willebrand disease type IIB. Because risks for mother and child vary so greatly according to the cause of thrombocytopenia, an accurate etiologic diagnosis is essential to ensure optimal therapeutic management.