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PubMed1999

Bleeding and activation of coagulation during and after transurethral prostatectomy: importance of the acute-phase response and prostate specific antigen?

OBJECTIVE: To evaluate the importance of coagulation activation in patients with benign prostatic hyperplasia, undergoing transurethral prostatic resection (TURP) and to examine whether changes in activity are related to blood loss, the circulatory entry of prostate specific antigen (PSA), operative trauma (resected tissue weight) and the inflammatory response, as assessed by C-reactive protein (CRP). PATIENTS AND METHODS: TURP was performed in 24 men and the weight of resected tissue and blood loss determined. The activation of coagulation was followed using new sensitive and specific assays, and the changes related to blood loss, the release of PSA, operative trauma and the acute-phase response. The area under the curve (AUC) for the measured quantities was used in correlation analysis. RESULTS: TURP was followed by a marked activation in coagulation. There was no correlation between the markers of coagulation and the operative blood loss, but the latter correlated with the weight of resected tissue (P=0.001). Postoperatively, the blood loss correlated with prothrombin fragment (F1+2; P=0.010), with thrombin-antithrombin complexes (TAT; P=0.024), and with the PSA concentrations (P=0.016) but not with fibrinogen. Serum concentrations of PSA increased significantly and the AUC in the operative period correlated with F1+2 (P=0.003) and TAT (P<0. 005), but postoperatively only with F1+2 (P=0.013). The weight of resected tissue correlated operatively with PSA (P=0.012) but not with the concentrations of F1+2 or TAT. Postoperatively, there was a correlation with the acute-phase proteins, CRP (P=0.005), fibrinogen (P=0.012) and with PSA (P=0.020). CONCLUSION: The operative blood loss is caused by surgical factors and the observed postoperative hypercoagulable state can be explained as a physiological response to bleeding, i.e. to secure haemostasis. The activity of coagulation was unrelated to operative trauma, but the acute-phase proteins were. The release of PSA into the circulation probably has an effect on blood coagulation.

Acute-Phase Reaction↗
PubMed2001

Calciphylaxis in two patients with end-stage renal disease.

Fatal calciphylaxis (CPX) occurred in two 71-year-old females both requiring haemodialysis for end-stage renal disease. Case 2 also had an associated follicular lymphoplasmocytoid lymphoma. Although laboratory tests disclosed normal coagulation parameters, this woman had a striking cutaneous histological picture of vessel thrombosis and finally died of disseminated intravascular coagulation. CPX is a rare but potentially life-threatening complication of renal failure. The clinical picture is primarily characterized by livedoid purpura with subsequent cutaneous ischaemia and painful ulcerations. Cutaneous ischaemic phenomena are sustained by a progressive process of vascular calcification and thrombosis involving small to medium size arteries of the dermis and subcutis. Although not yet clearly explained, the pathogenetic role of a predisposing hypercoagulability state is currently the most frequently considered hypothesis.

Aged↗
PubMed1999

Recurrent Mondor's disease resolved after exeresis of abdominal lipoma.

BACKGROUND: Mondor's disease is a rare disorder characterized by superficial thrombophlebitis, classically of the thoracic-epigastric and/or lateral thoracic veins. The etiopathogenesis of the disease is not entirely clear. OBJECTIVE: We report the case of a patient who presented with recurrent Mondor's disease involving the left abdominal wall along the thoracoepigastric vein as far as the ipsilateral iliac fossa where a lipoma was observed. METHODS: Surgical removal of the lipoma showed a close anatomical relationship between the affected veins and the neoformation. RESULTS: Follow-up after 1 year did not reveal any signs of relapse of the thrombophlebitis. CONCLUSION: Since primary or secondary factors leading to hypercoagulability states were not detected in our patient, we speculate that the interference of venous flow by the abdominal lipoma was probably implicated in the etiopathogenesis of the disease.

Abdominal Muscles↗
PubMedDate not supplied

Calciphylaxis: emerging concepts in prevention, diagnosis, and treatment.

Calciphylaxis is a small vessel vasculopathy involving mural calcification with intimal proliferation, fibrosis, and thrombosis. This syndrome occurs predominantly in individuals with renal failure and results in ischemia and necrosis of skin, subcutaneous fat, visceral organs, and skeletal muscle. The syndrome causes significant morbidity in the form of infection, organ failure, and pain. Mortality rates are high. In individuals with renal failure, risk factors for the development of calciphylaxis include female sex, Caucasian race, obesity, and diabetes mellitus. Many cases occur within the first year of dialysis treatment. Several recent reports demonstrate that prolonged hyperphosphatemia and/or elevated calcium x phosphorus products are associated with the syndrome. Protein malnutrition increases the likelihood of calciphylaxis, as does warfarin use and hypercoagulable states, such as protein C and/or protein S deficiency. Recent advances in diagnostic tools and therapeutic strategies have helped in the management of patients with calciphylaxis.

Calciphylaxis↗
PubMed2003

Management of venous thromboembolism during pregnancy.

The incidence of venous thromboembolism (VTE) probably increases 2-4-fold in pregnancy and is higher after a caesarean section than after vaginal delivery. Management of VTE in pregnancy is challenging. Many diagnostic tests are less accurate in pregnant than in non-pregnant patients and some radiologic procedures expose the fetus to ionizing radiation, although this can be reduced by taking appropriate precautions. Compression ultrasonography (CUS) is the test of choice for deep vein thrombosis (DVT), whereas for PE, V/Q lung scan is the first-line test, followed by CUS if the results are non-diagnostic. Anticoagulants that have been evaluated for the prevention and treatment of VTE in pregnancy include heparin and heparin compounds, and coumarin derivatives. When determining the optimal treatment regimens, it is important to consider: (i) the safety of the drug for the fetus and mother; (ii) the efficacy of the regimen; and (iii) the dose regimens for acute and secondary treatment, and during delivery and postpartum. Heparins are safer than coumarins for the fetus, as they do not cross the placental barrier. Heparins, particularly unfractionated heparin (UFH) and low molecular weight heparin (LMWH) tend also to be safer for the mother than other compounds. Of the two, LMWHs, although more expensive, are associated with lower rates of bleeding complications, and heparin-induced thrombocytopenia and osteoporosis, than UFH, and should therefore be the treatment of choice in VTE during pregnancy. Patients with prior VTE or a hypercoagulable state have an increased risk of VTE during pregnancy. Depending on the presence of one or both of these factors, clinical surveillance, with anticoagulant treatment where necessary, is recommended.

Anticoagulants↗
PubMed2004

Endoscopic ultrasound is a sensitive and specific test to diagnose portal venous system thrombosis (PVST).

OBJECTIVES: Thrombosis of the portal venous system (PVS) may complicate cirrhosis, pancreatitis, malignancies, and hypercoagulable states. Computed tomography (CT) scanning can diagnose thrombi present in the lumen of the PVS, but is probably insensitive. Endoscopic ultrasound (EUS) may be a more sensitive test for diagnosing PVS thrombosis (PVST). We sought to determine the accuracy of EUS for the diagnosis of PVST. METHODS: Using a retrospective analysis of patients' studies retrieved from a database at Massachusetts General Hospital, we determined the sensitivity and specificity of EUS in 16 patients with PVST and 29 without PVST as proven by surgery and/or CT scanning. All patients underwent a linear EUS exam of the PVS and the results of the EUS report were used as the basis of the study. RESULTS: The sensitivity of EUS for the finding of PVST was 81% in 13 of 16 patients and the specificity was 93% in 27 of 29 patients with an overall accuracy of 89% (40/45). In an additional group of 11 patients, EUS demonstrated the presence of a PVST that was not detected by CT scanning. CONCLUSION: Linear EUS is a highly sensitive and specific test for PVST.

Endosonography↗
PubMed1999

Activation markers of coagulation.

Advances in our understanding of the biochemistry of the haemostatic mechanism have led to the development of sensitive methods for measuring peptides, enzyme-inhibitor complexes, and enzymes that are liberated with the activation of the coagulation system in vivo. Studies employing these markers have provided important mechanistic information regarding haemostatic mechanism function both under normal conditions and in response to pathogenic stimuli. While assays for particular components can denote the presence of a 'biochemical' hypercoagulable state prior to the appearance of overt thrombotic phenomena, most of these markers thus far have not been shown to be useful in managing individual patients. Properly designed prospective studies will be required to determine whether these assay techniques will aid in the identification of patients predisposed to thrombotic events or the monitoring of antithrombotic therapy.

Animals↗
PubMed2001

Pulmonary medicine and palliative care.

Gynaecological malignancies affect the respiratory system both directly and indirectly. Malignant pleural effusion is a poor prognostic factor: management options include repeated thoracentesis, chemical pleurodesis, symptomatic relief of dyspnoea with oxygen and morphine, and external drainage. Parenchymal metastases are typically multifocal and respond to chemotherapy, with a limited role for pulmonary metastatectomy. Pulmonary tumour embolism is frequently associated with lymphangitic carcinomatosis, and is most common in choriocarcinoma. Thromboembolic disease, associated with the hypercoagulable state of cancer, is treated with anticoagulation. Inferior vena cava filter placement is indicated when anticoagulation cannot be given, or when emboli recur despite adequate anticoagulation. Palliative care has a major role for respiratory symptoms of gynaecological malignancies. Treatable causes of dyspnoea include bronchospasm, fluid overload and retained secretions. Opiates are effective at relieving dyspnoea associated with effusions, metatases, and lymphangitic tumour spread. Non-pharmacological therapies include energy conservation, home redesign, and dyspnoea relief strategies, including pursed lip breathing, relaxation, oxygen, circulation of air with a fan, and attention to spiritual suffering. Identification and treatment of gastroesophageal reflux, sinusitis, and asthma can improve many patients' coughs. Chest wall pain responds to local radiotherapy, nerve blocks or systemic analgesia. Case examples illustrate ways to address quality of life issues.

Aged↗
PubMed2001

Disseminated intravascular coagulation.

Healthy pregnancy is accompanied by changes in the haemostatic system which convert it into a hypercoagulable state vulnerable to a spectrum of disorders ranging from venous thromboembolism to disseminated intravascular coagulation (DIC). This latter is always a secondary phenomenon triggered by specific disorders such as abruptio placentae and amniotic fluid embolism due to release of thromboplastin intravascularly or endothelial damage resulting from pre-eclampsia and sepsis. In modern obstetric practice the most common cause is haemorrhagic shock with delay in resuscitation leading to endothelial damage. The initial management of massive obstetric haemorrhage is the same whether associated with coagulopathy initially or not. Low-grade DIC, associated with pre-eclampsia, is monitored haematologically by serial platelet counts and serum fibrin degradation products (FDPs). Supportive measures and removal of the triggering mechanism are the key to successful management. Outcome depends primarily on our ability to deal with the trigger and not on direct attempts to correct the coagulation deficit.

Abortion, Therapeutic↗
PubMed1996

Mesenteric venous thrombosis treated with urokinase via the superior mesenteric artery.

A 77-year-old man with a history of multiple surgically treated malignancies presented with increasing abdominal pain after eating. Computerized tomographic scan showed superior mesenteric vein and portal vein thrombosis. The patient was treated with selective superior mesenteric artery infusion of urokinase resulting in clinical improvement and near complete resolution of the mesenteric venous thrombosis. An underlying gastric malignancy was found and is believed to be the cause of the patient's hypercoagulable state. Direct infusion of urokinase into the superior mesenteric artery for treatment of mesenteric venous thrombosis is an alternative to surgery in selected patients and an alternative to the much more complicated delivery systems presently used.

Aged↗
PubMed2001

Role of acquired and hereditary thrombotic risk factors in colon ischemia of ambulatory patients.

BACKGROUND & AIMS: Hypercoagulable states may play an important role in the pathogenesis of colon ischemia. Aim of this study was to assess this hypothesis investigating the role of acquired and hereditary thrombotic risk factors in patients with definite diagnosis of colon ischemia. METHODS: We compared the frequency of antiphospholipid antibodies, protein C, protein S, and antithrombin deficiencies, factor V Leiden, prothrombin gene mutation G20210GA, and methylenetetrahydrofolate reductase C677T in 36 patients (23 men, 13 women; mean age, 64.8 years) with colon ischemia, 18 patients with diverticulitis, and 52 healthy controls. RESULTS: The prevalence of antiphospholipid antibodies was significantly higher in patients with colon ischemia compared with inflammatory and healthy controls (19.4% vs. 0% and 1.9%). Among genetic factors, only factor V Leiden was significantly associated with colon ischemia (22.2% vs. 0% and 3.8%). A combination of thrombophilic disorders was found in 25% of the cases. Overall, one or several prothrombotic abnormalities were present in 26 patients (72%). CONCLUSIONS: A comprehensive thrombophilic screening in colon ischemia reveals a congenital or acquired thrombophilic state in 72% of patients. Hereditary and acquired thrombotic risk factors may play an important role in the disease pathogenesis.

Ambulatory Care↗
PubMed2006

Vascular toxicity of antineoplastic agents.

Among the various deleterious effects of cancer chemotherapy, vascular toxicity is the least well recognized. This lack of recognition may be because the vasculotoxic phenomena are not unique to antineoplastic agents, can occur in patients without exposure to these agents, and the fact cancer itself may produce a hypercoagulable state. As a result, many vascular events either go unnoticed, are ignored, and/or are attributed to the underlying malignancy. Many antineoplastic therapies are associated with various vascular phenomena that range from simple phelibitis to lethal microangiopathy. Recognition of these events is important to minimize the morbidity and even prevent unnecessary deaths. Herein we review the vascular syndromes that have been reported in association with antineoplastic agents.

Animals↗
PubMed2001

Diabetic thigh muscle infarction in association with antiphospholipid antibodies.

BACKGROUND: Diabetic muscle infarction (DMI) is a rare complication of type 1 diabetes mellitus. DMI has a stereotyped clinical presentation and characteristic, though nonspecific, magnetic resonance imaging (MRI) and histologic findings. The etiology, however, remains controversial. OBJECTIVES: To present the first reported cases of DMI in association with positive antiphospholipid (aPL) antibody titers and to discuss the etiologic and pathogenic significance of the association between type 1 diabetes and aPL antibodies. METHODS: Descriptive case reports of 2 patients with DMI and positive aPL antibodies and a review of the relevant literature. RESULTS: Our 2 patients with DMI are female type-1 diabetics with end-organ microvascular complications who presented with an abrupt, painful swelling or mass of the thigh musculature. The diagnosis of DMI was based on the clinical picture and the findings on T2-weighted MRI and histologic evaluation. The first patient had a long history of known aPL antibodies in the setting of systemic lupus erythematosus. The second patient was only determined to be aPL positive after her recurrent episodes of DMI. The first patient was treated with anticoagulation and corticosteroids with relatively rapid resolution of symptoms. The second patient was treated with local débridement and supportive care with a resulting course of prolonged symptoms and recurrences. There are no controlled trials of the treatment of DMI. In the literature there is evidence for an increased prevalence of aPL antibodies in type 1 diabetic patients. The pathogenesis of DMI is poorly understood, but the hypercoagulable state often associated with aPL antibodies may play an important role. CONCLUSIONS/RELEVANCE: aPL antibodies may be involved in the pathogenesis of diabetic muscle infarction and could serve as an important target of therapeutic intervention, namely with anticoagulation.

Adult↗
PubMed2003

Applications of percutaneous mechanical thrombectomy in transjugular intrahepatic portosystemic shunt and portal vein thrombosis.

Portal vein thrombosis (PVT) is an uncommon cause for presinusoidal portal hypertension. PVT can be caused by one of three broad mechanisms: (1) spontaneous thrombosis when thrombosis develops in the absence of mechanical obstruction, usually in the presence of inherited or acquired hypercoagulable states; (2) intrinsic mechanical obstruction because of vascular injury and scarring or invasion by an intrahepatic or adjacent tumor; or (3) extrinsic constriction by adjacent tumor, lymphadenopathy or inflammatory process. Usually, several combined factors are necessary to result in PVT. The consequences of portal vein thrombosis are mostly related to the extension of the clot within the vein. Gastrointestinal bleeding from gastroesophageal varices is the most frequent presentation. Noninvasive imaging techniques are currently used for the screening of patients and the initial diagnosis of PVT. The invasive techniques are reserved for cases when noninvasive techniques are inconclusive, before percutaneous interventional treatment, or in preoperative assessment of patients who are candidates for surgery. Recanalization of the portal vein with anticoagulation alone may not be consistent or appropriate in highly symptomatic patients. Catheterization of the superior mesenteric artery (SMA) is helpful for diagnosis as well as for therapy by allowing the intra-arterial infusion of thrombolytic drugs in the same setting. Direct transhepatic portography allows precise determination of the degree of stenosis and extension within the portal vein, as well as pressure measurements. Thrombotic occlusions of the portal, mesenteric, and splenic veins can be managed by mechanical thrombectomy (MT) or pharmacologic thrombolysis. Underlying occlusions because of organized or refractory thrombus or fixed venous stenosis are best corrected by balloon angioplasty and stent placement. Access into the portal venous system can also be established through creating a transjugular intrahepatic portosystemic shunt (TIPS). Creating a TIPS is also important in the setting of PVT associated with cirrhosis to decompress portal hypertension and improve portal venous flow. PVT involving the portal, splenic, and/or mesenteric veins can also complicate a preexisting TIPS in which case the shunt can be readily used as therapy access. Several techniques may be used to recanalize the shunt and portal venous system, including thrombolytic therapy, balloon angioplasty/embolectomy, suction embolectomy, basket extraction of clots, and mechanical thrombectomy with a variety of devices. Advantages of MT include the potential to rapidly remove thrombus without the need for prolonged thrombolytic infusions, and reducing the potential life-threatening complications of thrombolytic therapy. Possible drawbacks include the risk of intimal or vascular trauma to the portal vein, which may promote recurrent thrombosis.

Humans↗
PubMed2001

Activation of coagulation and fibrinolysis in microsurgical reconstructions in the lower extremities.

Coagulation and fibrinolysis activities in relation to trauma, surgery and thrombosed microanastomoses were studied during free-flap surgery in eight patients with lower-extremity defects due to recent trauma or chronic ulcers. One patient had an intraoperative thrombosis, and three more patients required reoperations on the same day due to postoperative thromboses; one of these also required a second reoperation due to flap failure. The baseline level of fibrinogen was slightly elevated in all patients except one, and was significantly higher in the patients who underwent reoperation. At the end of the primary surgery, distinct thrombin generation (TAT and F1+2) was seen in three patients with excessive bleeding, and all three later underwent reoperations. One of these patients generated excessive thrombin on the eighth postoperative day, upon removal of a necrotic flap. Thrombin generation (F1+2) was also seen at baseline in the patient with the intraoperative thrombosis, and persisted on the first postoperative day. D-dimer at baseline was higher in patients with recent trauma, and in two of these, both of whom underwent reoperations on the same day, D-dimer remained high perioperatively. Resistance to fibrinolysis with increased PAI-1 levels was seen in these two patients at the time of reoperation. In all, TAT and F1+2 were associated with the threat of flap failure. A preoperative hypercoagulable state and excessive bleeding during the operation were predictors of reoperation. The markers for coagulation and fibrinolysis could be used preoperatively to target antithrombotic control, and postoperatively to detect the threat of flap failure. Meticulous haemostasis during surgery might help to diminish the need for reoperations.

Adult↗
PubMed2001

Acquired thrombophilic syndromes.

As the biochemical mechanisms of hypercoagulable states are revealed, the syndromes of venous thromboembolism have been increasingly associated with specific aberrations. Most of these changes involve an increase in procoagulant potential, for example, by activation of the coagulation cascade, or by a defect or decrease in natural inhibitors of clotting. Similar abnormalities of the fibrinolytic pathways may contribute, as can loss of inhibitory mechanisms of endothelial cells, as well as changes in vascular anatomy and rheologic patterns of blood flow. All of these factors can directly influence thrombus formation and/or the physiologic response to the thrombus.(1)

Humans↗
PubMed1996

Resistance to Activated Protein C: Comparison of Three Different PCR Methods for Detection FV R506Q.

Background: Resistance to activated protein C(APC) is the most prevalent identifiable risk factor for inherited thrombophilia. Over 90% of APC resistance results from a single point mutation in the Factor V gene. The mutation, termed FV R506Q of FV Leiden, predicts an abnormal Factor Va protein in which arginine, at amino acid position 506, is replaced by glutamine, rendering Factor Va resistant to proteolytic inactivation by APC, thus establishing a life long hypercoagulable state. The current study compared three different polymerase chain reaction (PCR)-based approaches for the detection of FV R506Q. Methods and Results: Sixty-seven patient blood samples were genotyped by (1) analyzing for loss of a Mnl I recognition site, an acquired restriction-fragment-length polymorphism (RFLP) due to FV R506Q; (2) primer-engineered RFLP wherein the presence of FV R506Q results in generation of a novel Nla III recognition site; and (3) allele-specific PCR. Sixty-five of 67 patient samples yielded concordant genotype results by all three PCR methods. Of the remaining 2 of the 67 patients, a "nondiagnostic" result was obtained for either allele-specific PCR or primer-engineered RFLP. Conclusions: A comparative analysis of 67 patient samples demonstrated that primer engineered RFLP and allele-specific PCR offer feasible alternative or confirmatory testing approaches to Mnl I RFLP for the detection of FV R506Q. A high degree of diagnostic concordance was observed for all three methods, and no false positive or negative results were observed with the Mnl I RFLP technique.

Journal Article↗
PubMed1999

The effect of fish oil on hypertension, plasma lipids and hemostasis in hypertensive, obese, dyslipidemic patients with and without diabetes mellitus.

We have recently reported that dietary fish oil supplementation (n-3) polyunsaturated fatty acid (PUFA) led to a reduction in blood pressure (BP) and serum triglycerides (TG), in addition to the normalization of the hypercoagulable state in subjects with obesity, hypertension and dyslipidemia without diabetes mellitus (OHD-DM). The aim of the present study was to explore the mechanism of this amelioration by comparing the previous results to those obtained from 19 subjects who, in addition to the conditions described above, also suffer from diabetes mellitus (OHD+DM) and proteinuria. In both the non-diabetic and diabetic groups, a similar reduction was observed in BP (from 158.7/80.8 to 146/72.9 mmHg, and from 157.6/83.2 to 141.9/75.6 mmHg, respectively, P<0.001) and TG levels (from 159.2 to 108.0 mg/dl and from 208.7 to 153.1 mg/dl, respectively, P<0.001). However, a favorable reduction in hemostasis parameters (platelet aggregation on extracellular matrix and (alpha2-antiplasmin) was only seen among the nondiabetic patients (from 12.1+/-4.9 to 4.2+/-3.2%, P<0.001). This difference may stem from a less efficient exchange between n-3 and n-6 PUFA in serum phospholipid of the OHD+DM patients. Overall, this 13-day fasting/refeeding method developed by us has proven to cause the rapid exchange of arachidonic acid for eicosapentaenoic acid. It appears to be an effective regimen for the reduction of cardiovascular risk factors (BP, TG and hemostatic variables) in OHD-DM patients and to a lesser extent in OHD+DM patients.

Aged↗