Fibrinolytic Split Products Research Articles

The Cause of Coagulopathy After Peritoneovenous Shunt for Malignant Ascites

Thirty-five patients with malignant ascites who received a peritoneovenous shunt were studied to determine the type and duration of postoperative coagulopathy. Coagulation factors were measured before and on the first and third day after the placement of a Denver peritoneovenous shunt; 1 to 10 L of ascites was removed at operation. Levels of platelets, antithrombin III, plasminogen, antiplasmin, fibrinogen, and factors V and VIII decreased by the first postoperative day but did not change further through the third day. The levels of fibrinolytic split products increased on day 1 but were lower by day 3. The platelet count reduction by the third day correlated with the hematocrit change (-0.031). The prothrombin and activated partial thromboplastin times remained normal postoperatively. The patterns of change were similar for patients with positive (n = 18) and negative (n = 17) ascites cytologic findings, with elevated (n = 24) and normal (n = 11) preoperative fibrinolytic split product levels, and elevated bilirubin value (greater than 25 mumol/L; n = 9), and no jaundice (n = 26). Bleeding did not occur. The data indicated that plasminogen-rather than thromboplastin-activated fibrinolysis occurred and that platelet reduction was largely dilutional. The reactions were not progressive when ascites was removed operatively.

Hemostasis in Pregnant Saudi Women

A cross-sectional study of various hemostatic variables was undertaken in women during the three trimesters of normal pregnancy. In the third trimester of pregnancy, there was significant elevation...

A functional photometric assay for plasma fibrinogen

We have developed a photometric assay for fibrinogen concentration. The sample is mixed with a snake venom enzyme (Batroxobin) and fibrin formation is recorded turbidimetrically at 334 nm. Reaction conditions are such that a linear increase in absorbance is obtained over a concentration range of fibrinogen from 80–700 mg/dl. Higher or lower ranges can be measured by adjusting the sample volume. Calibration is performed with a single standard. Precision and accuracy are comparable with the usual clinical chemical methods. Experiments with plasma samples digested with streptokinase showed that interference of fibrinolytic split products (FSP) is less than using the Clauss method. Large amounts of FSP in the sample, however, delay the increase in absorbance. This phenomenon can be utilized for the additional estimation of the FSP-content of the sample. Results obtained with the present method corresponded well with those obtained using the method of Clauss.

Envenomation by the Mojave rattlesnake ( Crotalus scutulatus scutulatus) in southern Arizona, U.S.A.

Fifteen cases of envenomation by the Mojave rattlesnake ( Crotalus scutulatus scutulatus) are reviewed. Systemic effects were observed in eight patients, consisting of early hypotension (3), decreased plasma fibrinogen (3) and platelets (2), elevated fibrinolytic split products (3) and eyelid ptosis (1). Local venom effects were most common and included swelling (15), ecchymosis (10), bleb formation (6) and necrosis (3). Effects upon neuromuscular transmission were neither common nor a clinical problem. Treatment consisted of i.v. crystalloid solution (15) and antivenin (12).

Serine proteases as mediators of radiographic contrast media toxicity.

Iodipamide, iodoxamine, iothalamate, diatrizoate, and ioxitalamate exhibit a dose-dependent prolongation of coagulation time of global and monospecific functional coagulation tests. This is due to an inhibition of fibrin polymerization induced by these contrast media. Furthermore, a dose-dependent generation of fibrinolytic split products by RCM was found. At low doses, biliary RCM cause hypercoagulation by binding to spontaneously existing fibrinolytic products. Biliary RCM cause a dose-dependent decrease of hemolytic complement activity and decrease of complement factors of C3, B, and, to a lesser extent, C4. Nephrotopic RCM do not show these effects. By crossed immunoelectrophoresis B and C3 split products were not detected after in vitro incubation of iodipamide in serum or EDTA-blood. In contrast, zymosan, inulin, and dextran sulfate incubation of sera readily resulted in Bb and C3b generation. The failure to demonstrate complement split products was not due to artifacts. As a working hypothesis unspecific binding of RCM to blood proteins followed by interference with antithrombin and antiplasmin inhibitor functions is proposed. Possibly other antiproteases might be involved too. This results in a lowering of the clinical manifestation threshold of coagulation and fibrinolysis. The mechanism of complement activation remains unclear, since it is not influenced by EDTA, aprotinin, steroids, or by specific sera depleted of prekallikrein, Hageman factor, C2, and gamma-globulins.

Disseminated Intravascular Coagulopathy

Disseminated intravascular coagulation is most common in children with bacterial septic shock, infants with severe respiratory distress syndrome, in giant hemangiomas, and in purpura fulminans. The diagnosis is suspected when purpuric bleeding and/or thrombosis occurs in those clinical settings known to have DIC associated with them. The coagulopathy is also suspected when the patient has thrombocytopenia and prolonged clotting times in coagulation screening tests (prothrombin time and partial thromboplastin time). Confirmation of the diagnosis requires further laboratory data. Although it would be ideal to have a complete analysis of all the coagulation factors, this is generally not universally available nor always necessary in all cases. In the absence of liver disease, the minimal criteria for diagnosis is the combination of thrombocytopenia, positive fibrinolytic split products, and hypofibrinogenemia (or prolonged thrombin time). In the presence of liver disease, reduced factor VIII and/or the presence of circulating soluble fibrin complexes would be needed to diagnose DIC. Once the diagnosis is established and the underlying illness identified and treated, the therapy of the DIC is generally supportive. Anticoagulation (heparin) management is rarely needed except in cases of purpura fulminans, where it can be lifesaving, and selected cases of giant hemangioma or malignancy. In cases of septic shock and in severe RDS, successful management of the shock and the respiratory failure will cause the DIC to disappear without the use of anticoagulation.

Disseminated Intravascular Coagulopathy

Disseminated intravascular coagulation is most common in children with bacterial septic shock, infants with severe respiratory distress syndrome, in giant hemangiomas, and in purpura fulminans. The diagnosis is suspected when purpuric bleeding and/or thrombosis occurs in those clinical settings known to have DIC associated with them. The coagulopathy is also suspected when the patient has thrombocytopenia and prolonged clotting times in coagulation screening tests (prothrombin time and partial thromboplastin time). Confirmation of the diagnosis requires further laboratory data. Although it would be ideal to have a complete analysis of all the coagulation factors, this is generally not universally available nor always necessary in all cases. In the absence of liver disease, the minimal criteria for diagnosis is the combination of thrombocytopenia, positive fibrinolytic split products, and hypofibrinogenemia (or prolonged thrombin time). In the presence of liver disease, reduced factor VIII and/or the presence of circulating soluble fibrin complexes would be needed to diagnose DIC. Once the diagnosis is established and the underlying illness identified and treated, the therapy of the DIC is generally supportive. Anticoagulation (heparin) management is rarely needed except in cases of purpura fulminans, where it can be lifesaving, and selected cases of giant hemangioma or malignancy. In cases of septic shock and in severe RDS, successful management of the shock and the respiratory failure will cause the DIC to disappear without the use of anticoagulation.

Blood Coagulation, Fibrinolysis and their Inhibitors Studies on Patients with Cancer

Fourteen parameters concerning coagulation, fibrinolysis and their inhibitors were measured in the 170 patients with various malignancies, including 68 cases of stomach cancer, 22 lung cancer, 21 colon and rectum cancer, 14 renal and urinary tract cancer, 9 primary hepatic cancer, 8 uterus and ovary cancer, 4 breast cancer and 19 others.Their parameters were platelet count, plasma fibrinogen level, prothrombin time, thrombotest, hepaplastintest, serial thrombin time, fibrinolytic split products, plasma plasminogen, ethanol gelation test, protamin sulfate test, cryofibrinogen, serum antithrombin III, serum α1 antitrypsin and serum α2 macroglobulin. Cases treated with anti-tumor agents were excluded in this study.Increased FDP in 52% (86 cases), prolonged serial thrombin time in 80%, positive paracoagulation tests and decreased antithrombin III were suggestive of increased activity of coagulation and fibrinolysis. The term of intravascular coagulation and fibrinolysis syndrome (ICF syndrome) was applied to the condition of increased FDP over 20μg/ml.And on the basis of fibrinogen (normal 200-400mg/dl) ICF syndrome was divided into 3 groups as following.Group I; hyperfibrinogenemiaPlatelet was increased, antithrombin III was decreased, plasminogen was normal or increased and paracoagulation tests tended to be positive. This conditions was defined as over compensated ICF syndrome, which was 16% (14 cases) of total ICF syndrome.Group II; normal fibrinogenemiaPlatelet was normal, antithrombin III was decreased, plasminogen was normal and paracoagulation test were less frequently positive. This condition was compensated ICF syndrome, which 59% (51 cases).Group III; hypofibrinogenemiaPlatelet was decreased, also antithrombin III and plasminogen were decreased. Paracoagulation tests were more frequently positive. This condition was defined as decompensated ICF syndrome, which was 25% (21 cases).Marked decrease of fibrinogen, platelet antithrombin III and plasminogen was observed in some patients in this group. DIC with bleeding tendency clinically observed belongs to this group.We concluded that it was significant to devide ICF syndrome due to malignancy into 3 groups on the basis of blood coagulation and fibrinnolysis for the management of patients with malignancy.

Fibrinolytic Degradation Products in Urine of Anticoagulated Transplant Patients

A study of the level of urinary fibrinolytic split products in 14 renal transplant patients who received oral anticoagulants postoperatively revealed a tendency toward increased levels of fibrinolytic split products that were temporally related to graft rejection. The amount of fibrinolytic split products in the urine was positively related to the severity of rejection as well as to the final status of the allograft. Thus, the urinary level of fibrinolytic split products, as determined by the latex-coated particle test, can be used as an indicator of the course of warfarin-anticoagulated patients after renal allografting.

Fibrinolytic split products (FSP) and ethanol gelatin test in preoperative evaluation of patients with prostatic disease

Fibrinolytic split products (FSP) and ethanol gelatin test in preoperative evaluation of patients with prostatic disease

Fibrinolytic split products. A clinicopathological correlative study in adults with lupus glomerulonephritis and various renal diseases.

Fibrinolytic split product (FSP) levels were correlated with renal biopsy results in 25 adults with lupus glomerulonephritis and 23 adults with other renal diseases. The FSP levels were elevated in 42 of the 48 patients. Other coagulation studies showed increased plasma fibrinogen levels in 29 of 33 patients, positive ethanol gelation reactions, and prolonged prothrombin, thrombin, or plasma clot times. All platelet counts were normal or slightly elevated. In glomerular capillaries of lupus nephritis patients, elevated FSP levels correlated best with fibrinoid presence, and, to a lesser degree, with fibrin. There were no relationships between FSP levels and glomerular lesions in patients with other renal diseases. Although there was reliable clinical and pathologic evidence for intravascular coagulation in these renal disease patients, the pathogenetic role of intravascular coagulation in destructive and progressive renal lesions in man remains unknown.

Pitfalls of the microtiter system for serial dilutions and standardization using radioiodinated albumin.

The hemagglutination inhibition immunoassay and the staphylococcal clumping technic for determining fibrinolytic split products both utilize the microtiter system. The quality control of this system, using 131I-labeled albumin, is described. Three dropper pipettes were found to have errors, based on an expected volume of 25 µ l., of –7.6 to 14.4% (mean 3.5%). Eight transfer pipettes were found to contain volumes larger than the expected 25 µ l.; the errors ranged from 6.4 to 14.0% (mean 9.9%). The proper use of the microtiter system and the accuracy of doubling dilutions are discussed. The technic has inherent pitfalls but, if performed properly, gives reproducible results.

Protamine sulfate test for fibrin monomers.

A procedure utilizing protamine sulfate to demonstrate the presence of fibrin monomers is described. The procedure is unaffected by heparin and by fibrinolytic split products. Interference by high levels of plasmin, however, was suggested. The possibility of precipitating protein fractions other than fibrin monomers has been lessened by utilizing a low concentration of protamine sulfate (0.9%) and a temperature of 37 C. This method was more sensitive and less subject to interference than two other procedures used to demonstrate fibrin monomers. Its application in differentiating disseminated intravascular coagulation from primary fibrinolysis is discussed.

39. Fibrinolytic system in infants of low birth weight and/or short gestational period

The aims of this investigation were: (1) to study fibrinolytic activity and the development of the different factors of the fibrinolytic system from early “prematurity” up to term and (2) to study the changes, if any, of these factors in ifants with postnatal asphyxia, idiopathic respiratory distress syndrome (IRDS), and intracranial hemorrhages. The material consisted of 197 infants in the 25th to 43rd gestational week. Approximately half of the material served as a “control material” to the rest of the infants with postnatal asphyxia and IRDS. Blood was obtained from a catheter in the umbilical artery or vein. Serial sampling was performed in one part of the material. Determinations were made of: fibrinolytic activity on fibrin plates, fibrinolytic split products (FSP) in serum and in serum with addition of ϵ-aminocaproic acid (EACA), fibrinogen, plasminogen, antiplasmin, α2-macrogtobulin, inhibitors of urokinase activation of plasminogen. Plasminogen and α2-macroglobulin increased significantly with increasing length of gestation, while the other factors were at the same levels as in full term newborns throughout. Fibrinolytic activity was demonstrated even in the smallest infants and also in infants which developed IRDS. It was high in some infants with severe hypoxia. FSP in serum-EACA were studied by serial sampling and were found in infants with severe hypoxia and acidosis. The various factors of the fibrinolytic system are sufficiently developed in preterm infants which are capable of producing fibrinolytic activity. The findings argue against the assumption that IRDS is due to a primary deficiency of the fibrinolytic system. It rather lends support to the hypothesis of an increased fibrinolysis in infants with hypoxia and acidosis.

On fibrinolytic split products in serum and urine in uraemia.

Serum (in 84 cases) and urine (in 33 cases) from patients with acute and chronic uraemia were examined immunoelectrophoretically for fibrinolytic split products (FSP). FSP in serum were found in 9 out of 12 acute cases, in 12 out of 40 conservatively treated chronic cases, and in 13 out of 32 chronic cases, on maintenance haemodialysis. Also in urine FSP tended to be more common in acute than in chronic cases. In conservatively treated chronic cases the occurrence of FSP varied with the clinical activity of the disease and the degree of uraemia.There were no definite signs of systemic fibrinolysis or disseminated intravascular coagulation in cases with FSP, so that the split products must derive from dissolution of local fibrin deposits. The demonstration of high molecular weight FSP both in serum and urine or only in the urine and in the absence of post-renal disease strongly suggests the presence of such local fibrin deposits in the kidney.Examination of serum and urine for FSP may be useful in the inve...

A Case of Acute Glomerulonephritis and Severe Uraemia, Treated with Heparin and Corticosteroids

A case of acute oliguric glomerulonephritis and severe uraemia treated with heparin is described.A 13-year-old girl developed streptococcal glomerulonephritis 4 weeks after having had a throat infection. The patient developed oliguria and rapidly progressive uraemia. Initially the coagulation status showed fibrinolytic split products in serum with low fibrinolytic activity and normal fibrinogen content. A local fibrin deposit with secondary fibrinolysis was suspected and heparin was given. In the course of combined treatment with penicillin, prednisolone and heparin, the patient improved. After 6 weeks renal function was normal and proteinuria had disappeared. Percutaneous renal biopsy, 6 months after the patient had fallen ill, showed only sequelae after glomerulonephritis and no signs of activity. It is concluded that, if there are signs of local fibrin deposits, treatment with heparin should be considered in cases of acute glomerulonephritis with severe uraemia and that the determination of fibrinolyti...

Kidney transplantation and fibrinolytic split products in serum and urine.

Kidney transplantation and fibrinolytic split products in serum and urine.

Platelets and the triggering mechanism of intravascular coagulation.

Summary The ability of platelets to trigger intravascular coagulation was studied by infusing a suspension of frozen‐thawn homologous platelets into rabbits pretreated with either saline or Thorotrast. Each animal received during a period of 30 min an amount of platelets at least equivalent to the number of circulating platelets in a normal animal of the same weight. The infusion of platelet material did not trigger fibrinogen consumption in saline‐pretreated animals. In Thorotrast‐pretreated animals, however, the platelet suspension produced significantly increased disappearance of [125I]fibrinogen, moderate decreases in the fibrinogen level, significant falls in factors V and VIII, but no increase in fibrinolytic split products. None of the animals developed the generalized Shwartzman reaction. We conclude that platelets contain weak procoagulant activity which was effectively cleared by the reticuloendothelial system in the normal animal. Depression of the phagocytic capacity by Thorotrast prior to the infusion unmasked moderate intravascular coagulation.

Pneumococcal sepsis with generalised Shwartzman reaction.

Abstract. A patient in hospital developed acute pneumococcal sepsis during which lesions typical of the generalised Shwartzman reaction appeared. The patient went into shock, showed signs of respiratory distress, she had haemorrhagic necrosis of the skin and transient anuria but ultimately recovered. Detailed investigation of the haemostatic and fibrinolytic systems revealed rapid consumption of platelets, decreased prothrombin and factor V, and a large increase of fibrinolytic split products.

Fibrinolysis in newborns.

SummaryThe fibrinolytic system was studied in 207 normal fullterm newborns during the first 5 days of life. A high, but rapidly decreasing plasminogen activator activity was found during the first 4 hours in umbilical vein blood in all of the children studied. The activity in the cord blood was lower and cannot be regarded as representative of the child. Fibrinolytic split products were demonstrated in large and rapidly decreasing amounts in serum samples without the addition of EACA but in at most small amounts in serum when EACA was added at sampling. These findings confirm the high plasminogen activator activity at birth which rapidly falls and furthermore show that there are no significant amounts of split products in vivo in the newborn. The plasminogen level was decreased in accordance with previous investigations. The high activator activity is counterbalanced by adequate inhibitory protection with an increase of the α2‐macroglobulin and inhibitors of plasminogen activation and the adult content of antiplasmin. The mean fibrinogen values in the first 48 hours of life are in the lower part of the normal range, but increase on the third day to a significantly higher level.