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.

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.].

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.

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.

Síndrome de plaquetas pegajosas. Reporte de 2 casos en el servicio de Cirugía Oral y Maxilofacial Pediátrica de la Fundación Hospital de la Misericordia / Sticky platelet syndrome. A report of 2 cases

El síndrome de plaquetas pegajosas (SPP) es un trastorno que se traduce en una serie de fenómenos protrombóticos a expensas de hiperagregabilidad plaquetaria. Es un trastorno raro y, a pesar de que puede ser identificado eficazmente mediante agregometría plaquetaria, se desconoce la etiología. Algunas publicaciones indican que el 20% de los eventos vaso-oclusivos arteriales corresponden a casos asociados al SPP. El SPP constituye un trastorno inusual; los pocos reportes oscurecen la prevalencia de esta entidad. Tiene implicación en el fracaso de colgajos libres e injertos por la formación de microtrombos. El propósito de este artículo es presentar 2 casos remitidos al Servicio de Cirugía Oral y Maxilofacial Pediátrica. Adicionalmente, se presenta una revisión actualizada sobre la etiología y diagnóstico de esta condición (AU)

Sticky platelet syndrome (SPS) is a disorder that is associated with a series of arterial and venous prothrombotic events due to of platelet hyperaggregability. It's a rare condition, and even though there are efficient platelet aggregometry methods to diagnose the disorder, the underlying pathophysiology remains unclear. Some publications suggest that approximately 20% of vaso-occlusive events are of SPS origin. SPS is an unusual condition; the limited number of reports contributes to the lack of documentation regarding this syndrome. SPS is associated with maxillofacial free flap and graft failures due to thrombi formation. The purpose of this article is to present 2 cases of SPS seen in the Pediatric Oral and Maxillofacial Surgery Department together with a review on the etiology and diagnostic features of SPS (AU)

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.

C-reactive protein and fibrin clot strength measured by thrombelastography after coronary stenting.

Inflammation is implicated in the progression of coronary artery disease and the molecular processes of inflammation and thrombosis are closely intertwined. Elevated levels of C-reactive protein (CRP) have been associated with an elevated risk of adverse ischaemic events after coronary stenting and hypercoagulability. Heightened whole blood clot strength measured by thrombelastography (TEG) has been associated with adverse ischaemic events after stenting. We intended to examine the relationship of CRP to plasma fibrin clot strength in patients after coronary stenting. Plasma fibrin clot strength was measured by TEG in 54 patients 16-24 h after undergoing elective percutaneous coronary intervention (PCI). Coagulation was induced in citrated plasma by addition of kaolin and CaCl2. Plasma levels of CRP and fibrinogen were measured by enzyme-linked immunoassay. Increasing quartiles of CRP were associated with increasing levels of maximal plasma fibrin clot strength measured by TEG (P < 0.001) and increasing BMI (P = 0.04). Patients in the highest quartile of CRP had significantly higher maximal fibrin clot strength (G) than the patients in the lowest quartile (G: 3438 ±â€Š623 vs. 2184 ±â€Š576 dyn/cm, P < 0.0001). Fibrinogen concentration was not significantly different across quartiles of CRP (P = 0.97). Patients with established coronary artery disease undergoing coronary stenting who have elevated CRP after PCI exhibit heightened maximal plasma fibrin clot strength as compared with those with low CRP. Thrombotic risk associated with elevated CRP may be linked to procoagulant changes and high tensile fibrin clot strength independent of fibrinogen concentration.

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.

Silent cerebral infarct in child patients with beta thalassaemia intermedia.

There are numerous reports that patients with thalassemia are faced with hypercoagulability leading to vascular disorders. One of these complications is known as a silent infarct, defined as a small infarct detected by cerebral imaging but without any neurological symptoms. Since it has a progressive nature, it is of vital importance because it may lead to symptomatic cerebrovascular accidents in the future. Twenty-two children with thalassemia intermedia were enrolled into the study and MRI scans were performed. All demographic data and clinical features of the patients were obtained during the follow-up period. In addition to the patients, 13 healthy controls were included to compare serum anticoagulant levels with those of the thalassemia intermedia patients. Four of the patients were found to have silent cerebral infarcts (SCIs). The lesions involved varying amounts of the deep cerebral white matter and sub-cortical areas. One patient showed 'net line' filling defects within the ambient cistern on MRI images corresponding to moyamoya vessels. Three patients had undergone splenectomy, and three were transfused irregularly and had less than six transfusions per year. More importantly, protein C levels were lower and platelet levels were significantly higher in the patient group compared with controls. We were not able to find any association between SCI and transfusion number or splenectomy. However, of the total patients four thalassemia intermedia patients had SCI in early childhood and this is an unusual finding. In order to verify the findings, further studies must be conducted involving larger numbers of patients.

Recurrent pediatric thrombosis: the effect of underlying and/or coexisting factors.

The objective of this study was to evaluate the underlying diseases, thrombus localization, and other risk factors in pediatric patients with recurrent thrombosis in order to obtain a sense of early awareness of the possible recurrences. We retrospectively evaluated both inherited and acquired thrombophilic risk factors in children with recurrent thrombosis that were diagnosed and treated at Hacettepe University, School of Medicine, Department of Pediatric Hematology, Ankara, Turkey. Both congenital and acquired risk factors associated with recurrent thrombosis, and treatment modalities were analyzed in detail. Among 569 children with thrombosis, 32 (5.6%) presented with recurrent thrombosis. Median age at first presentation in these 32 patients [11 women (34.4%) and 21 men (65.6%)] was 132 months. In all, 29 (90.6%) of the 32 patients had an underlying chronic disorder: the most common of which was congenital heart disease [n = 11 (34.4%)]. At presentation intracardiac localization, including the entrance of the inferior and superior vena cava, was observed in 10 of the patients (31.2%). Thrombosis recurred at the same location in 15 (47%) patients and at a different location in 17 (53%). Median time interval between the first and second episode of thrombosis was 6.5 months (range: 1-180 months). Considering both acquired and congenital thrombophilic factors, three (9.3%) patients, four (12.5%) patients, and 14 (43.8%) patients had five, four, and three risk factors, respectively. More than half of the patients had elevated plasma FVIII (>150 IU/dl) and D-dimer (>0.5 mg/ml) levels. Thrombectomy was performed in three patients with organized, chronic intracardiac thrombus. Tissue plasminogen activator (t-PA) was used more frequently to treat recurrence than the first event (15.6 vs. 28.1%) and consequently the complete resolution rate was higher (40 vs. 77.7%) at the second event. Thrombi partially resolved in 11 of the patients during the initial episode and in 10 patients during recurrence (34 vs. 32%). In all, 29 (87.5%) patients were using prophylaxis at the time of recurrence. [coumadin (n = 16), low molecular weight heparin (n = 12) and aspirin (n = 1)]. In total, four patients (12.5%) died because of their underlying disorders and six (18.7%) developed postthrombotic syndrome during the follow-up. Recurrent thrombosis should be expected, especially in cases with congenital heart disease, incomplete thrombus resolution, and elevated plasma FVIII/D-dimer levels. In the light of this knowledge we suggest aggressive treatment for pediatric patients with a high risk of recurrent thrombosis.

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.

Prevention and treatment of hormone-associated venous thromboembolism: a patient management approach.

Given the known increased risk of venous thromboembolism (VTE) associated with both oral contraceptive (OC) use and hormone replacement therapy (HRT), it is important to address questions about the prevention and management of hormone-associated VTE. Specifically, the objectives of this article are as follows: (1) to provide suggested clinical management approaches for the primary and secondary prevention of VTE for women with thrombophilia; (2) to provide suggested clinical management approaches for the primary and secondary prevention of VTE in the perioperative period for women taking OC or HRT; and (3) to provide practical management approaches for frequently encountered clinical scenarios relating to duration of treatment for hormone-associated VTE.