Evidence Of Consumptive Coagulopathy Research Articles

Recognition of a Kawasaki Disease Shock Syndrome

We sought to define the characteristics that distinguish Kawasaki disease shock syndrome from hemodynamically normal Kawasaki disease. We collected data prospectively for all patients with Kawasaki disease who were treated at a single institution during a 4-year period. We defined Kawasaki disease shock syndrome on the basis of systolic hypotension for age, a sustained decrease in systolic blood pressure from baseline of > or =20%, or clinical signs of poor perfusion. We compared clinical and laboratory features, coronary artery measurements, and responses to therapy and analyzed indices of ventricular systolic and diastolic function during acute and convalescent Kawasaki disease. Of 187 consecutive patients with Kawasaki disease, 13 (7%) met the definition for Kawasaki disease shock syndrome. All received fluid resuscitation, and 7 (54%) required vasoactive infusions. Compared with patients without shock, patients with Kawasaki disease shock syndrome were more often female and had larger proportions of bands, higher C-reactive protein concentrations, and lower hemoglobin concentrations and platelet counts. Evidence of consumptive coagulopathy was common in the Kawasaki disease shock syndrome group. Patients with Kawasaki disease shock syndrome more often had impaired left ventricular systolic function (ejection fraction of <54%: 4 of 13 patients [31%] vs 2 of 86 patients [4%]), mitral regurgitation (5 of 13 patients [39%] vs 2 of 83 patients [2%]), coronary artery abnormalities (8 of 13 patients [62%] vs 20 of 86 patients [23%]), and intravenous immunoglobulin resistance (6 of 13 patients [46%] vs 32 of 174 patients [18%]). Impairment of ventricular relaxation and compliance persisted among patients with Kawasaki disease shock syndrome after the resolution of other hemodynamic disturbances. Kawasaki disease shock syndrome is associated with more-severe laboratory markers of inflammation and greater risk of coronary artery abnormalities, mitral regurgitation, and prolonged myocardial dysfunction. These patients may be resistant to immunoglobulin therapy and require additional antiinflammatory treatment.

Treatment of factor XI inhibitor using recombinant activated factor VIIa

A 30-year-old female with severe factor XI deficiency of 0-2% acquired factor XI inhibitor following many infusions for fresh frozen plasma (FFP) for surgical procedures starting at 4 years of age. Seven months before this inhibitor was diagnosed, surgery was complicated by prolonged bleeding resistant to FFP, requiring epsilon aminocaproic acid (EACA) and surgical packing. The inhibitor was measured at 2.2 Bethesda units, 7 months since the last FFP. The inhibitor was confirmed as specific anti-XI and anti-XIa binding by patient's IgG to immobilized factor XI and factor XIa from whole plasma and purified IgG. For repair of a painful anterior cruciate ligament (ACL) defect she was given recombinant factor VIIa (rVIIa) at 90 mug kg(-1), starting one-half hour preoperatively and continued every 2 h for 8 h when haemostasis was complete. Thereafter the rVIIa was given every 3 h for two doses, and then every 4 h for four doses at which time she was discharged on EACA which was continued for 6 days. There was excellent haemostasis during and following the surgery. There was no evidence of consumptive coagulopathy, with no change in the fibrinogen, platelet count, or D-D dimer; and no increase of platelet factor 4, beta-thromboglobulin, or prothrombin fragment F 1.2. The thrombin-antithrombin complex increased over baseline after 24 h. There was no postoperative deep vein thrombosis or pulmonary embolus. In this patient with a factor XI inhibitor, the recombinant factor VIIa was effective and safe, ensuring adequate haemostasis with no thrombotic complications. This product which was designed for patients with inhibitors to factor VIII or factor IX, and factor VII deficiency, has now been given successfully to four patients with factor XI inhibitors.

Novel treatment modalities: new platelet preparations and substitutes.

Keywords: platelets; platelet substitutes; platelet haemostatic function; blood substitutes; platelet function

Kasabach-Merritt Syndrome-Associated Kaposiform Hemangioendothelioma Successfully Treated With Cyclophosphamide, Vincristine, and Actinomycin D

The authors introduced a successful trial of a chemotherapy regimen to treat refractory thrombocytopenia and pain caused by a rare kaposiform hemangioendothelioma that had been refractory to corticosteroids. A 6-year-old Latina girl with diffuse petechiae, constant pain and edema in her right lower extremity, and severe thrombocytopenia was brought for treatment. Physical examination revealed a large mass in the right lower extremity. The surgical specimen resected earlier in Mexico showed kaposiform hemangioendothelioma, an extremely rare vascular tumor that is frequently associated with consumptive coagulopathy and lymphangiomatosis. Corticosteroid therapy in Mexico had been ineffective in controlling the tumor size, pain, or thrombocytopenia. The patient was brought to the United States because of a rapidly enlarging tumor and intractable leg pain, causing inability to ambulate. Laboratory examinations revealed profound thrombocytopenia and evidence of consumptive coagulopathy. Because of the rapidly enlarging lesion, it was decided to give six cycles of a chemotherapy regimen consisting of vincristine, cyclophosphamide, and actinomycin D (VAC). The patient responded to the first cycle of chemotherapy with partial reversal of the thrombocytopenia. The additional five cycles of the same chemotherapy regimen resulted in complete resolution of thrombocytopenia and significant improvement of the pain and edema in the right lower extremity. A follow-up imaging study 9 months later revealed a marked decrease in size of the vascular tumor. Inoperable kaposiform hemangioendothelioma unresponsive to corticosteroids can be successfully treated with chemotherapy.

Persistently Perplexing Purpuras: Thrombotic Thrombocytopenic Purpura and Immune Thrombocytopenic Purpura

Letters1 November 1994Persistently Perplexing Purpuras: Thrombotic Thrombocytopenic Purpura and Immune Thrombocytopenic PurpuraDorothea Zucker-Franklin, MDDorothea Zucker-Franklin, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-121-9-199411010-00032 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The recent report by Olenich and Schattner [1] of a case considered to represent postpartum TTP did not provide sufficient data to permit this diagnosis. Of the usual manifestations of TTP—thrombocytopenia, microangiopathic hemolytic anemia, neurologic symptoms, fever, and renal dysfunction—the patient in question seemed to have only two. Apparently, no hypertension, neurologic symptoms, or evidence of consumption coagulopathy were noted. A description of a skin or mucosal biopsy specimen confirming the clinical impression by showing aneurysmal dilatation at arteriocapillary junctions and hyaline deposits was also absent [2]. Unquestionably, this patient had thrombocytopenia and hemolytic anemia. We previously ...

Overwhelming Postsplenectomy Infection Presenting as Acute Lower Limb Ischemia—A Case Report

This report describes acute ischemia of the right lower extremity as the first sign of overwhelming postsplenectomy infection (OPSI) in a sixty-five-year-old man with known peripheral vascular disease two months after gastrectomy and splenectomy for gastric cancer. While emergency arterial bypass was being con sidered, the patient developed generalized peripheral vasoconstriction together with clinical and laboratory evidence of consumption coagulopathy and meta bolic acidosis. The possibility of OPSI was suggested and he was accordingly managed in the intensive care unit. A blood culture grew Streptococcus pneumo niae. The patient died of overwhelming pneumococcal sepsis with marked hemodynamic instability and multiorgan dysfunction four days after admission. The onset of acute lower limb ischemia was an early sign of OPSI in this patient with preexisting peripheral vascular disease. This sign has not been pre viously reported.

An unusual complication in a gravida with factor IX deficiency: Case report with review of the literature

Factor IX deficiency (hemophilia B, Christmas disease) is an X-linked recessive coagulation disorder. It occurs in one out of every 25,000-30,000 male births and requires even rarer genetic circumstances for phenotypic expression in females. We report the occurrence of a large, late-trimester subchorionic hematoma in a gravida with factor IX deficiency and with laboratory evidence of consumptive coagulopathy during treatment. The patient was managed conservatively and had a successful outcome at term. The only four reported cases of antepartum management of factor IX deficiency in the English literature are reviewed.

Clinical Pathologic Alterations Associated with Subcutaneous Administration of Recombinant Human Interleukin-4 to Cynomolgus Monkeys

Recombinant human interleukin 4 (rhuIL-4) is a candidate for the treatment of refractory cancer based on its potential to enhance immune function. Recombinant human IL-4 was administered subcutaneously at 0, 1, 5, or 25 micrograms/kg/day for 28 days with a 14-day recovery to male and female cynomolgus monkeys as part of the preclinical safety evaluation. Clinical pathologic changes related to treatment with rhuIL-4 were evidence of consumptive coagulopathy, erythrocyte fragmentation, lymphocytosis, and lymphocyte morphologic changes indicative of marked antigenic or mitogenic stimulation, mild eosinophilia and neutrophilia, hypoalbuminemia, hypocholesterolemia, and hypertriglyceridemia. Based on data obtained after the 14-day recovery period, the clinical pathologic changes associated with rhuIL-4 administration were considered to be reversible.

Pre-clinical toxicity of Il-4: A model for studying protein therapeutics

The purpose of this presentation was to review issues and findings in the pre-clinical development and evaluation of recombinant human protein therapeutics. Since human cytokines and lymphokines are endogenous proteins, their pre-clinical development and evaluation would seem straightforward and theor toxicities minimal. Unfortunately, the pre-clinical development of this class of agents has been problematic and confounding. Some of the clinical toxicities and pharmacodynamics have been predicted by the pre-clinical evaluation and others have not. Some molecules are species specific which limits species selection for pre-clinical evaluation. Other confounding issues include: route of exposure, synergy of toxicity with other lymphokines, length of study design, immunogenicity, predictiveness of pre-clinical evaluation and iatrogenic toxicities. An approach used by SWPRD in the evaluation of this class of molecules was discussed. Insight gained during the pre-clinical and clinical development of these molecules should simplify the further development of protein therapeutics that follow. Specific studies with recombinant human interleukin-4 (rhuIL-4) were reviewed in detail as part of a pre-clinical safety evaluation. Native IL-4 has properties that exemplify many of the immune recognition-induced lymphokines and is produced principally by activated T-lymphocytes CD4 +. It is a co-factor in B-cell proliferation and enhances ex vivo B-cell expansion and is believed to be a candidate for the treatment of refractory cancer based on this immune enhancement ability. rhyIL-4 is a 15,400 molecular weight cytokine produced in a yeast expression system. The unique species specificity of this lymphokine led to its ultimate evaluation in a non-human primate species. rhuIL-4 was administered subcutaneously (B.I.D.) at doses of 0, 1, 5 or 25 μg/kg/day for 28 days with a 14 day recovery to cynomolgus monkeys. Clinical pathology changes related to treatment were evidence of consumptive coagulopathy, lymphocytosis and lymphocyte morphologic changes indicative of marked antigenic or mitogenic stimulation, mild eosinophilia and neutrophilia, hypoalbuminemia, hypocholesterolemia, and hypertryglyceridemia. Histomorphologic evaluation revealed proliferation and inflammatory vascular lesions with eosinophil infiltration which principally affected the arterial tree, granulocytic hyperplasia, seminiferous tubular atrophy and splenic congestion. After 2 weeks of recovery, granulocytic hyperplasia was not observed and the vascular lesions occured with an overall lower incidence. The arteritis may be a direct pharmacodynamic effect of rhuIL-4 on vascular smooth endothelial cells possibly related to enhanced adhesion molecule expression. The antigenicity of this molecule for cynomolgus monkeys was also demonstrated and appeared to alter the pharmacokinetics of the protein drug substance at the end of the exposure period. The pre-clinical safety evaluation of rhuIL-4 has proven an interesting molecule to illustrate several of the confounding issues associated with the pre-clinical development of lymphokines.

Heparin cofactor II in adults and infants with thrombosis and DIC

Heparin cofactor II (HC II) was measured by a chromogenic activity assay in normal preterm infants (gestational age, 28-36 weeks; n = 17; 29% +/- 11.5 [mean +/- 1 SD], range 11-51), normal full-term infants (n = 18; 49% +/- 6.6 [mean +/- 1 SD], range 36-58), and normal adults (n = 38; 101% +/- 14 [mean +/- 1 SD], range 73-130). Normal children attained adult levels at approximately 5 to 7 months of age. The lower values in preterm and term infants most likely reflect immature liver function. Neither adults and children with a history of thrombosis with prior negative evaluation (n = 74), patients with documented protein C and protein S deficiency (n = 4), nor sick infants without evidence of consumptive coagulopathy (n = 15) had significantly lower levels of HC II activity. Infants with disseminated intravascular coagulation (n = 2) had strikingly lower levels of HC II activity.

Exhausted platelets in patients with malignant solid tumors without evidence of active consumption coagulopathy

Twenty-four patients with various types of tumors and without evidence of consumption coagulopathy (normal routine coagulation tests) were investigated for intraplatelet ATP, ADP, serotonin, beta-thromboglobulin and platelet factor 4; the percentage of light circulating platelets was also determined. Evidence for an acquired storage pool defect was found in seven patients (29%) without any correlation with the clinical status, the presence of metastases, platelet count or fibrinogen level. These results show that exhausted platelets are commonly encountered in cancerous patients even in the absence of consumption coagulopathy. The precise mechanism of this abnormality remains to be established.

Postmortem manifestations of echovirus 11 sepsis in five newborn infants

Five cases of fatal neonatal echovirus type 11 infection were observed in the Boston area during the summer and fall of 1979. Four of the mothers experienced gastroenteritis with fever and abdominal cramps late in the third trimester of pregnancy. The clinical course of each case was characterized by jaundice, hepatosplenomegaly, and progressive hepatic failure; all five infants were severely hypotonic. At autopsy massive hepatic and adrenal hemorrhage and necrosis, with evidence of consumption coagulopathy, were found. Echovirus type 11 was isolated from various sites before and after death. The histopathologic features and epidemiologic aspects of these cases are briefly discussed.

DEFICIENCIES OF PROTEIN C, AN INHIBITOR OF BLOOD COAGULATION

Protein C is a vitamin-K-dependent plasma glycoprotein that when activated inhibits coagulation by selectively inactivating the active forms of factor V and factor VIII. A specific antiserum to protein C has been raised, and plasma protein C levels have been measured by means of an electroimmunoassay in several physiological and pathological conditions. In 60 healthy adults there were no differences in protein C related to age or sex; protein C levels ranged from 72 to 139% of values in a normal plasma pool. Low levels were found in 12 healthy full-term newborn infants; the levels in 20 women in the last trimester of normal pregnancy were no different from those in healthy non-pregnant women. In 58 patients with chronic liver diseases protein C levels were lower than those in healthy subjects, in degrees roughly proportional to the severity of the disease. Protein C levels were very low in 21 patients with the disseminated intravascular coagulation syndrome, particularly in those who had evidence of consumption coagulopathy. Very low levels were also found, however, in 20 patients with adult respiratory distress syndrome without consumption coagulopathy. Acquired defects of protein C developed after surgery in the patients operated on for malignancies, after major abdominal operations for benign conditions, and also after relatively minor procedures such as appendicectomy and hernia repair. These findings indicate that protein C deficiencies occur in several conditions associated with increased tendency to thrombosis.

Haemodynamic data, blood gas measurements and coagulation disorders in acute respiratory failure of patients with chronic lung disease (author's transl)

24 subjects with chronic obstructive pulmonary disease were investigated in the course of acute respiratory failure defined by hypoxaemia, hypercapnia and respiratory acidosis. Haemodynamic data of right heart catheterization and coagulation tests were particularly studied. 12 of these subjects had right heart failure defined by a rise of right ventricular end-diastolic pressure above 10 Torr. Coagulation tests brought evidence of consumption coagulopathy in 8 patients, 7 of whom had right heart failure. Data suggest a significant correlation between right heart failure and coagulation disorders in patients with acute exacerbation of chronic obstructive pulmonary disease. These disturbances, accompanied by reduction of pulmonary vascular area, could be in part related to the presence of microthrombi in pulmonary arterial vessels.

Meningococcemia and Treated With

Several publications have recently emphasized the relationship between fulminant meningococcemia and consumption coagulopathy.1-3Patients exhibiting meningococcal infection with intravascular coagulation and consumption of clotting factors have an extremely poor prognosis. Their course is usually characterized by irreversible shock. Treatment of the consumption coagulopathy with heparin has failed to alter the course of the irreversible shock and hemorrhagic tendency.1,2Winkelstein et al3have recently reported successful treatment of three patients with heparin sodium and dextran 70. These patients had laboratory evidence of consumption coagulopathy, but were free of purpura. This report concerns a patient with fulminant meningococcemia, shock, extensive purpura, and consumption coagulopathy, who was successfully treated with heparin and dextran 70. The use of dextran as a volume expander was necessitated by the refusal of the patient, a Jehovah's Witness, to accept transfusions or blood products. In addition, dextran was utilized because of antithrombotic properties which may