Role of platelets in thrombin generation amongst patients with non-transfusion-dependent thalassaemia.

Non-transfusion-dependent thalassaemia (NTDT) is associated with a hypercoagulable state with thrombotic risk highest after splenectomy. Various mechanisms have been proposed. Although an antiplatelet agent is commonly recommended as thromboprophylaxis in NTDT, the role of platelets contributing to this hypercoagulable state is not well-defined. This study aims to evaluate the role of platelets contributing to hypercoagulability in NTDT patients using thrombin generation (TG). Platelet-rich (PRP) and platelet-poor plasma (PPP) were collected from NTDT patients (n = 30) and normal controls (n = 20) for TG measurement and compared. Controls had higher endogenous thrombin potential (ETP) in PPP (1204.97 nM.min vs 911.62 nM.min, p < 0.001) and PRP (1424.23 nM.min vs 983.99 nM.min, p < 0.001) than patients. Patients' mean normalized ETP ratio [{PRP ETP (patient)/PPP ETP (patient)}/{mean PPP ETP (controls)/mean PPP ETP (controls)}], demonstrated that the presence of platelet does not alter ETP (mean ratio 0.97, 95% CI 0.93-1.02, equivalence defined as 10%). Types of thalassaemia, splenectomy, and severity of liver iron overload did not significantly influence patients' ETP in PPP and PRP by multivariate analysis. Platelets did not increase the TG potential of NTDT patients. Instead of being hypercoagulable, our NTDT patients were hypocoagulable by ETP measurement, although this could not be conclusively demonstrated to correlate with their iron overloading state giving rise to reduced synthesis of coagulation factors. The guideline recommendations for thromboprophylaxis with antiplatelet agents in similar NTDT patients should be re-examined.

Cerebral venous thrombosis following spinal surgery in a patient with Factor V Leiden mutation.

Cerebral venous thrombosis is a devastating event leading to high mortality and morbidity rates. We present a case of cerebral venous thrombosis that occurred following spinal surgery in a patient with Factor V Leiden mutation and G1691A heterozygosity. Possible prevention and treatment strategies have been discussed.

Prophylaxis for thromboembolic disease and evaluation for thrombophilia.

Patients treated with total hip or knee arthroplasty are at risk for venous thromboembolic disease. Laboratory evaluation of thrombophilia can help to better identify patients at higher risk for venous thromboembolic disease, and newer methods that test for genetic factors continue to evolve; however, more research is needed to justify routine testing for thrombophilia. Research studies have yielded differing results in determining the most appropriate prophylactic regimen. Both pharmaceutical and mechanical treatments are commonly used for prophylaxis. New pharmacologic prophylaxes include the Xa inhibitor rivaroxaban and the thrombin inhibitor dabigatran etexilate. The newest mechanical device used to prevent venous thromboembolism is a miniature, mobile, battery-operated pneumatic system called Continuous Enhanced Circulation Therapy. The American College of Chest Physicians guidelines and the American Academy of Orthopaedic Surgeons clinical guideline were reviewed to directly compare specific agents and balance the risks of venous thromboembolism. Future studies for venous thromboembolic prophylaxis will continue to evaluate new oral agents, improved pneumatic compression devices, and improved methods to decrease bleeding in the immediate postoperative period.

[Modern methods of diagnosis of thrombophylic states and complex treatment of patients with thrombotic complications of severe forms of varicose disease].

Actual issues of surgical treatment of patients, suffering complications of severe forms of varicose disease of the lower extremities (VDLE) are discussed. The causes of unsatisfactory results of treatment in patients, suffering varicothrombophlebitis (VTHPH), the main of which--absence of the only one tactics for operative treatment and anticoagulant therapy, were analyzed. The results of patients examination, suffering thrombotic complications of severe forms of VDLE, while its recurrent course, in conjunction of VTHPH and thrombosis of deep veins of the lower extremities, using diagnostic complex "PLR genetics thrombophilia", are adduced. Differential tactics of treatment in patients, suffering severe forms of VDLE, while various localization of thrombotic process, concerning the presence of thrombophilic states, is proposed.

[Thrombotic complications of severe forms of varicose disease: modern approach to diagnosis and treatment of hereditary thrombophilia and immunohistochemical peculiarities of vascular wall].

Experience of treatment of 176 patients, suffering thrombotic complications of severe forms of the lower extremities varicose disease (VDLE), was analyzed. In 20 patients, suffering varicothrombophlebitis (VTHPH) in severe forms of VDLE, morphological and immunohistochemical changes in the venous wall and surrounding tissues were studied. There were examined 28 patients, in whom thrombotic complications of the VDLE have had occurred, using diagnostic complex "PLR genetics thrombophilia". Recurrent course of thrombotic complications and coexistence of VTHPH and thrombosis of deep veins have had constitute the main criterion of such patients selection. The groups of patients, suffering severe forms of VDLE, were delineated, depending on thrombotic process localization, differentiated tactics of their surgical treatment was proposed.

Platelet hyperreactivity: report of a case with catastrophic arterial thrombosis in a child.

Platelet hyperreactivity is an important but under-recognized cause of idiopathic arterial thrombosis. We describe a case of arterial thrombosis in a previously healthy 12-year-old girl after minor trauma to the knee, resulting in lower extremity amputation. Family history was positive for arterial and venous thrombosis, but an extensive work-up for the usual inherited thrombophilia risk factors was negative. The patient was eventually diagnosed with platelet hyperreactivity and remains on life-long antiplatelet therapy.Consideration of platelet hyperreactivity in the evaluation of unusual arterial thrombotic events allows for targeted therapy, potential avoidance of future events, and timely screening of family members.

Perioperative Coagulation Changes in Total Pancreatectomy and Islet Autotransplantation.

OBJECTIVES: Thrombotic complications after total pancreatectomy with islet autotransplantation (TPIAT) are common. However, the systemic changes to coagulation in the perioperative period have not been well studied. Our objective was to evaluate the derangements in coagulation in the perioperative period for this procedure. METHODS: This was a prospective observational study of patients undergoing elective TPIAT for chronic pancreatitis. Multiple methods of evaluating coagulation, including 2 viscoelastic assays and standard laboratory assays were obtained at defined intraoperative and postoperative intervals. RESULTS: Fifteen patients were enrolled. Laboratory values demonstrated initial intraoperative hypercoagulability before significant systemic anticoagulation after islet infusion with heparin. Hypercoagulability is again seen at postoperative days 3 and 7. Subgroup analysis did not identify any major coagulation parameters associated with portal vein thrombosis formation. CONCLUSIONS: Apart from the immediate period after islet cell and heparin infusion, patients undergoing TPIAT are generally hypercoagulable leading to a high rate of thrombotic complications. Portal vein thrombosis development had minimal association with systemic derangements in coagulation as it is likely driven by localized inflammation at the time of islet cell infusion. This study may provide the groundwork for future studies to identify improvements in thrombotic complications.

Preventing postsurgical venous thromboembolism: pharmacological approaches.

The use of antithrombotic drugs for the prevention of venous thromboembolism (VTE) in patients undergoing surgery is presently based on solid principles and high-level scientific evidence. This article reviews current strategies of pharmacological thromboprophylaxis. The level of VTE risk following surgery depends on a variety of factors that the surgeon should take into account, including the type of surgery and the presence of additional risk factors, such as elderly age and cancer. In patients undergoing minor general surgery, early mobilization is sufficient as prophylaxis, whereas in those undergoing major general surgery, thromboprophylaxis with low molecular weight heparin (LMWH), low-dose unfractionated heparin, or the pentasaccharide fondaparinux is recommended. Patients undergoing major orthopedic surgery have a particularly high risk of VTE, and routine thromboprophylaxis with LMWH, fondaparinux, or a vitamin K antagonist (international normalized ratio target: 2.0 to 3.0) is the standard of care in this group of patients. Recently, two new oral anticoagulants, rivaroxaban (a factor Xa inhibitor) and dabigatran etexilate (a direct thrombin inhibitor) have been licensed to be used for thromboprophylaxis after orthopedic surgery in Europe. Mechanical methods of thromboprophylaxis (compression stockings, intermittent pneumatic compression, vena cava filters), not discussed in detail in this review, should always be considered in patients at high thrombotic risk, in association with the pharmacological strategies, or in cases of contraindications to anticoagulants, as in patients or procedures at high risk of bleeding.

Long-term Anticoagulation Prevents Progression of Stages I and II Primary Osteonecrosis of the Hip in Patients With Familial Thrombophilia.

The authors prospectively assessed long-term anticoagulation outcomes (≥3 years) for 9 patients meeting 4 inclusion criteria: pretreatment Ficat stage I or II primary hip osteonecrosis (ON), factor V Leiden or prothrombin G20210A heterozygosity, no contraindication to anticoagulation, and 90-day participation in an initial enoxaparin 60 mg/d protocol. The primary endpoint was prevention of hip collapse (Ficat stage III or IV). The secondary endpoint was pain relief. After 90 days of enoxaparin 60 mg/d, anticoagulation was continued for 8 patients: 4 receiving warfarin (international normalized ratio targeted to 2 to 2.5; 11.5, 13, 14.5, and 21 years), 1 receiving enoxaparin 120 mg/d (11.5 years), and 3 receiving novel oral anticoagulants (5, 6, and 8 years). Radiographs were obtained before treatment; at 3 to 4, 6 to 8, and 12 to 14 months; and then annually. By selection, 8 patients had factor V Leiden heterozygosity and 1 had prothrombin G202010A heterozygosity. Of their 13 hips (Ficat I or II at entry), 12 remained Ficat I or II after 12±5 years (range, 5.5-21 years) of continuous anticoagulation and follow-up; 1 hip radiographically normalized. None of the 13 hips progressed to collapse (Ficat III or IV). Six patients became symptom free after the first 3 months of receiving enoxaparin, 1 after 6 months of anticoagulation, and 1 after 10 months of anticoagulation; all 8 patients remained symptom free with anticoagulation. Anticoagulation for primary hip ON before hip collapse in patients with familial thrombophilia may change the natural history of ON because most untreated patients with ON have joint collapse and total joint replacement within 2 years of original symptoms. [Orthopedics. 2020;43(4):e208-e214.].

Coagulation dynamics and platelet functions in obstructive jaundiced patients.

BACKGROUND: All of the body systems are affected by increased levels of bilirubin. The aim of this study is to investigate the function of platelets and clotting dynamics in patients with obstructive jaundice. METHODS: Liver function tests, serum CRP, PT, PTT and hemogram were measured in 23 patients with obstructive jaundice. Thromboelastography (TEG) was done for the evaluation of coagulation dynamics, while platelet function assay (PFA 100) was used to evaluate platelet functions. Blood samples were obtained at two occasions, before the drainage and 3 weeks after the relief of the obstruction. RESULTS: Hypercoagulation was detected in 80% of patients. Maximum strength, elasticity, coagulation indices of the clot were correlated with increased concentrations of direct bilirubin. Although maximum strength of coagulum usually represents increased activity of platelet function, membrane closure times with PFA 100 were found to be prolonged in 30% of patients, reduced values were determined in 17% of patients. No demonstrable effect on coagulation parameters and platelet function were detected after drainage procedures regardless of modality. CONCLUSIONS: Even though there is a general assumption about the increased bleeding tendency in obstructive jaundiced patients, we could not demonstrate reduced clotting activity by measuring with either PFA or TEG. On the contrary we observed tendency for hypercoagulation independent of increased prothrombin times. The most probable cause of this effect is the increased activity of fibrin polymers on platelet membrane.

Sacral preservation in cauda equina syndrome from inferior vena cava thrombosis.

Acute cauda equina syndrome can occur due to a variety of causes. Inferior vena cava (IVC) thrombosis has been reported as the causal source of this phenomenon twice in the relevant literature, both cases of which presented in a form complete with a component of bowel and/or bladder dysfunction. The authors report an atypical case of cauda equina syndrome in a patient in a hypercoagulable state with an extensive IVC thrombosis, resulting in acute paraparesis in the absence of incontinence or perineal anesthesia. An increasing number of prophylactic and/or therapeutic IVC filters placed in the perioperative period should engender an increased clinical suspicion for IVC thrombosis in patients presenting with acute paraparesis.

Thalassemia and hypercoagulability.

Thalassemia is a congenital hemolytic disease caused by defective globin synthesis resulting in decreased quantity of globin chains. Although the life expectancy of beta-thalassemia patients has markedly improved over the last few years, patients still suffer from many complications of this congenital disease. The presence of a high incidence of thromboembolic events, mainly in beta-thalassemia intermedia, has led to the identification of a hypercoagulable state in these patients. In this paper, we review the molecular and cellular mechanisms leading to hypercoagulability in beta-thalassemia, with a special focus on thalassemia intermedia being the group with the highest incidence of thrombotic events as compared to other types of thalassemias. We also discuss the recommendations for thrombosis prophylaxis in these patients.

[Phlebothrombosis and pulmonary thromboembolism in patients with thrombophilia].

A study was made of the course of phlebothrombosis ana pulmonary thromboembolism in 54 patients with thrombophilia. Of these, 23 patients had factor la resistance to protein C, 15 presented with antiphospholipid syndrome, four with protein C deficit, one with protein S deficit, three with antithrombin III deficiency, and three patients with hyperhomocysteinemia. Five patients presented with the following combined forms of thrombophilia: thrombophilia due to protein C deficit and antiphospholipid syndrome; protein C deficit and hyperhomocysteinemia; protein C and antithrombin III deficit; factor Va resistance to protein C and hyperhomocysteinemia; antiphospholipid syndrome and hyperhomocysteinemia. Thrombosis of the inferior vena cava (IVC) was present in 52 and PTE in 27 patients, The recurrence of phlebothrombosis was recorded in 40 (76.9%), that of PTE in 12 (44.4%) patients. The time elapsed between disease exacerbations accounted for one month to nine years, the number of recurrences constituted two to 6. Initially, thrombosis in three patients was located in lower limb saphenous veins, in 18 in the tibial and femoral veins, in 29 in the femoral and iliac veins; two patients presented with femoroiliocaval phlebothrombosis. The recent control examination revealed thrombosis of the saphenous veins in two patients. In ten patients, thrombosis was located in the tibiofemoral segment, in 19 patients, it was discovered in the femoroiliac and in two cases, in the femoroiliocaval segment. During observation period, venous thrombosis in the previously intact lower limb developed in nine (16.7%) patients. Thrombosis of other vessels inclusive of the organ ones was present in 14 (25.9%) patients. Of these, seven patients had thrombosis of the arteries of the upper and lower limbs: in four cases, it was located in the system of the IVC and in two cases, in the mesenterial arteries; ischemic stroke was recorded in two cases, thrombosis of the portal vein in one, and myocardial infarction was also marked in one case. In view of different hemostatic changes underlying the development of venous thromboses and PTE, we carried out differentiated therapy applying anticoagulants, platelet inhibitors, and transfusions of quickfrozed plasma. In acute femoroiliac and caval thromboses and PTE, 40 patients were provided implantation into the IVC of the cava filter <>. After cava filter implantation 16 patients developed tnrombosis of the IVC. Embolism to the cava filter occurred in seven patients. In three cases, it terminated in occlusion of the IVC and in the remaining cases, in its recanalization. Over the period one to six years, occlusive thrombi of the IVC underwent recanalization in 11 patients. Analysis of the course of phiebothrombosis and PTE in patients with thrombophilia made it possible to define situations that require its goal-oriented search. It is demonstrated that it is advisable to implant the cava filter <> to the permanent position in thromboses of the femoral, iliac veins and of the IVC as well as in PTE.

Reduction of coagulability state one year after bariatric surgery.

BACKGROUND: Obese patients are in a hypercoagulable state relative to normal-weight patients. Low-grade inflammation may be a key factor for this condition. OBJECTIVES: Our study aimed to compare the coagulability state of morbidly obese patients before and 1 year after bariatric surgery (BS) using the Thrombin Generation (TG) test, a validated method to assess coagulation in vitro. SETTING: University hospital. METHODS: All patients undergoing BS between September 1, 2014 and April 30, 2015 were eligible for this prospective study (n = 42). Two distinct reagents were used for TG initiation based on the tissue factor concentration (Reagents LOW and HIGH). The main outcomes were endogenous thrombin potential (ETP) and peak height of TG. The rate of follow-up after one year was 97%. RESULTS: One year after surgery, %weight loss was 32.5±8.4%; CRP decreased from 9.0 (3.7-12.9) to 1.1 (0.3-2.8) mg/mL (P<.001) and fibrinogen from 4.2±.8 to 3.5±.8 g/L (P<.001). The ETP (%) decreased from (108.0 (95.0-117.0) to 78.0 (71.0-98.0) (P<.001) (LOW reagent) and from 113.0 (103.0-134.0) to 96.0 (86.0-107.0) (P<.001) (HIGH reagent). Peak height (%) decreased from (117.0 (92.0-139.0) to 82.0 (70.0-111.0) (P = .003) (LOW reagent) and from 106.0 (96.0-118.0) to 97.0 (87.8-105.2) (P = .003) (HIGH reagent). CONCLUSION: Our study shows a significant reduction in TG potential one year after BS in morbidly obese patients. Reduction of low grade inflammation may be one of the underlying mechanisms.

Stroke following Glenn anastomosis in a child with inherited thrombophilia.

The optimal anticoagulation following Fontan operation and its modifications remain controversial and it is even less well defined as regards patients with inherited thrombophilia. We present a case of a child with bidirectional Glenn anastomosis for double inlet left ventricle that suffered a stroke despite aspirin prophylaxis; the patient was combined homozygous for prothrombin G20210A mutation and for methylenetetrahydrofolate reductase C677T mutation as well. The family history was positive for fetal loss and premature cardiovascular disease. Large-scale studies are needed to evaluate whether carriers of thrombophilia mutations need more intense thromboprophylaxis.

[Pulmonary arterial thromboembolism and thrombophilias: optimization of diagnostics and treatment].

The subjects of the study were 94 patients with pulmonary arterial thromboembolism (PATE). The prevalence of thrombophilic conditions (TC) among these patients was studied, and their role in the development of an unfavorable clinical course of PATE was evaluated. A three-year prospective study revealed that pre-thrombotic conditions had been diagnosed in 90% of PATE patients. There is a strong correlation between an unfavorable course of PATE and the presence of isolated or combined genetic mutations, or a combination of those with an increase of factor VIII level, and a high titer of cardiolipin antibodies with a mutation in factor V gene. Occurrence of PATE in patients less than 40 years of age who suffer from an idiopathic type of venous thrombosis and have a family background of thrombophilic conditions, which requires a detailed hematological examination, is a predictor of unfavorable course of PATE in the post-hospital period. Purposeful pharmaceutical correction of thrombophilic conditions lowers the frequency of venous thrombosis recurrence from 39% to 17%, the frequency of cava-filter thrombosis recurrence from 24% to 3.7%, and the frequency of PATE recurrence from 15% to 5.6%.