Hemorrhagic State Research Articles

Detrimental hemodynamic effects of assisted ventilation in hemorrhagic states

Our goal was to demonstrate explicitly that lower-frequency positive-pressure ventilation not only preserves adequate oxygenation and acid-base status in hemorrhagic states, but also that "normal" or higher respiratory rates significantly compromise hemodynamics, even with moderate degrees of hemorrhage. Eight intubated pigs (ventilated with 12 mL/kg tidal volume, 28% FIO2, respiratory rate = 12 breaths/min) were hemorrhaged to <65 mm Hg of systolic blood pressure. Respiratory rates were then sequentially changed every 10 mins to 6, 20, 30, and 6 breaths/min. With respiratory rates at 6 breaths/min, all subjects maintained pH of >7.25 and SaO2 of >99% while increasing systolic blood pressure (mean, 65-84 mm Hg; p < .05), time-averaged coronary perfusion pressure (50 +/- 2 to 60 +/- 4 mm Hg; p < .05), and cardiac output (2.4 to 2.8 L/min; p < .05). With respiratory rates of 20 and 30 breaths/min, systolic blood pressure (73 +/- 4 and 66 +/- 5 mm Hg, respectively), coronary perfusion pressure (47 +/- 3 and 42 +/- 4 mm Hg), and cardiac output (2.5 and 2.4 L/min) diminished. When returned to 6 breaths/min, systolic blood pressure (95 mm Hg), coronary perfusion pressure (71 + 6 mm Hg), and cardiac output (3.0 L/min) improved significantly (p < .05 for all comparisons). After moderate hemorrhage, animals maintain adequate oxygenation and acid-base status with lower-frequency respiratory rates, whereas increasingly higher respiratory rates progressively and significantly impair hemodynamics. Current ventilatory protocols for trauma resuscitation should be re-examined and considered a possible cause of worsened clinical outcomes and unrecognized confounded study results.

Peroxynitrite decreases hemostasis in human plasma in vitro.

Coagulopathy has been associated with clinical scenarios that involve reactive nitrogen species such as peroxynitrite (OONO-). Further, OONO- decreases tissue factor and fibrinogen function in vitro. Thus, we hypothesized that exposure of plasma to the OONO- generated with 3-morpholinosydnonimine (SIN-1), a molecule that produces both nitric oxide and superoxide, would result in a decrease in hemostatic function via diminished coagulation protein activity. Hemostatic function of plasma exposed to SIN-1 (0, 1, 5, and 10 mM for 60 min at 37 degrees C) was assessed with thrombelastography, activated partial thromboplastin time, and prothrombin time in the presence or absence of superoxide dismutase (SOD) or an OONO- scavenger. SIN-1 exposure resulted in a significant (P < 0.05), dose-dependent decrease in plasma hemostatic function and concurrent significant (P < 0.05) decreases in activities of factor VII, factor VIII complex, and factor X. Fibrinogen concentration was not affected by SIN-1. Antithrombin and protein C activity also decreased significantly (P < 0.05). Coincubation with SOD or an OONO- scavenger significantly (P < 0.05) attenuated SIN-1 mediated changes in hemostasis and procoagulant/ anticoagulant activity. We conclude that OONO- may decrease hemostatic function in human plasma by nitration of key procoagulants and that OONO- may play a significant role in hemorrhagic states.

Confounding hemodynamic effects of assisted ventilation in hemorrhagic states

Confounding hemodynamic effects of assisted ventilation in hemorrhagic states

Isquemia e reperfusão hepática total associada ao estado de choque hemorrágico controlado: efeitos no seqüestro de neutrófilos no fígado do rato

OBJETIVO: O propósito deste trabalho experimental foi estudar os efeitos da isquemia e reperfusão hepática total sobre o acúmulo de neutrófilos no fígado de ratos, em condições de normalidade e submetidos ao estado de choque hemorrágico controlado. MÉTODO: Trinta e dois ratos Wistar, machos, foram divididos em quatro grupos de oito animais cada: grupo Controle, submetido à laparotomia com um período de 60 minutos de observação; grupo Choque, submetido a choque hemorrágico controlado (PAM = 40 mmHg, 20 min.) seguido de reposição volêmica (Ringer lactato + sangue, 3:1) e reperfusão (60 min.); grupo Pringle, submetido a isquemia hepática total (15 min.) e reperfusão (60 min.); grupo Total submetido a choque hemorrágico controlado (15 min.) seguido de reposição volêmica (Ringer lactato + sangue, 3:1) mais isquemia hepática total (15 min.) e reperfusão (60 min.). A dosagem do lactato arterial e déficit de base foram utilizados para caracterizar o estado de choque hemorrágico com baixa perfusão tecidual. Após a morte dos animais, procedeu-se à contagem de neutrófilos no tecido hepático. RESULTADOS: Na contagem de neutrófilos no fígado o grupo Pringle diferiu dos grupos Choque e Total, os quais não diferiram entre si (Controle 10,30±3,20; Choque 13,94±2,84; Pringle 7,00±3,40; Total 12,45±3,65). CONCLUSÃO: Em ratos submetidos a estado de choque hemorrágico controlado, associado à isquemia hepática total de 15 minutos, seguido de 60 minutos de reperfusão, não ocorreu acúmulo significativo de neutrófilos no fígado.

Emergency ventilatory management in hemorrhagic states: elemental or detrimental?

A study was performed to demonstrate that slower respiratory rates (RRs) of positive-pressure ventilation can preserve adequate oxygenation and acid-base status in hemorrhagic states, whereas "normal" or higher RRs worsen hemodynamics. Eight swine (ventilated with 12 mL/kg tidal volume, 0.28 Fio(2); RR of 12 breaths/min) were hemorrhaged to < 65 mm Hg systolic arterial blood pressure (SABP). RRs were then sequentially changed every 10 minutes to 6, 20, 30, and 6 breaths/min. With RRs at 6 breaths/min, the animals maintained pH > 7.25/Sao(2) > 99%, but increased mean SABP (from 65 to 84 mm Hg; p < 0.05), time-averaged coronary perfusion pressure (CPP) (from 50 +/- 2 to 60 +/- 4 mm Hg; p < 0.05), and cardiac output (Qt) (from 2.4 to 2.8 L/min; p < 0.05). With RRs of 20 and 30 breaths/min, SABP (73 and 66 mm Hg), CPP (47 +/- 3 and 42 +/- 4 mm Hg), and Qt (2.5 and 2.4 L/min) decreased, as did Pao(2) and Paco(2) (< 30 mm Hg), with p < 0.05 for each comparison, respectively. When RR returned to 6 breaths/min, SABP (95 mm Hg), CPP (71 +/- 6 mm Hg), and Qt (3.0 L/min) improved significantly (p < 0.05). After even moderate levels of hemorrhage in animals, positive-pressure ventilation with "normal" or higher RRs can impair hemodynamics. Hemodynamics can be improved with lower RRs while still maintaining adequate oxygenation and ventilation.

Understanding the complete blood count with differential

The complete blood count (CBC) with differential is one of the most common laboratory tests performed today. It gives information about the production of all blood cells and identifies the patient's oxygen-carrying capacity through the evaluation of red blood cell (RBC) indices, hemoglobin, and hematocrit. It also provides information about the immune system through the evaluation of the white blood cell (WBC) count with differential. These tests are helpful in diagnosing anemia, certain cancers, infection, acute hemorrhagic states, allergies, and immunodeficiencies as well as monitoring for side effects of certain drugs that cause blood dyscrasias. Nurses in the perianesthesia arena are frequently challenged to obtain and evaluate all or parts of the CBC as a part of the patient's preoperative, intraoperative, and postoperative assessments. An enhanced understanding of this laboratory test is essential to providing quality care. © 2003 by American Society of PeriAnesthesia Nurses.

Isquemia e reperfusão hepática total associada ao estado de choque hemorrágico controlado: efeitos no seqüestro de neutrófilos no pulmão do rato

OBJETIVO: Estudar os efeitos da isquemia e reperfusão hepática total sobre acúmulo de neutrófilos no interstício pulmonar de ratos, em condições de normalidade e submetidos ao estado de choque hemorrágico controlado. MÉTODOS: 32 ratos Wistar, machos, foram divididos em quatro grupos de oito animais cada: grupo Sham, submetido aos procedimentos padrões com um período de 60 minutos de observação; grupo Choque, submetido a choque hemorrágico controlado (PAM = 40 mmHg, 20 min.) seguido de reposição volêmica (Ringer lactato + sangue, 3:1) e reperfusão (60 min.); grupo Pringle, submetido a isquemia hepática total (15 min.) e reperfusão (60 min.); grupo Total submetido a choque hemorrágico controlado (15 min.) seguido de reposição volêmica (Ringer lactato + sangue, 3:1) e reperfusão (60 min.). Após o sacrifício dos animais, procedeu-se à contagem de neutrófilos no interstício pulmonar. RESULTADOS: Os valores encontrados para contagem de neutrófilos no interstício pulmonar indicaram que, os animais dos grupos Pringle, Total e, também, do grupo Choque, não diferiram dos animais do grupo Sham com valores de (Sham 21,08± 14,12; Choque 35,15± 18,74; Pringle 19,78± 15,38; Total 23,90± 16,37) (p=0.253) CONCLUSÃO: Em ratos submetidos a estado de choque hemorrágico controlado associado a isquemia hepática de 15 minutos, seguida de 60 minutos de reperfusão, não ocorreu acúmulo significativo de neutrófilos no interstício pulmonar.

Thrombocytopenic purpura after hepatitis B vaccine

OBJECTIVE: To demonstrate a case of idiopathic thrombocytopenic purpura after hepatitis B vaccine and drive attention to this possible relation when other causes have been excluded.METHODS: Description of a case of a patient who was 1 month and 16 days old and presented petechiae and ecchymoses one week before she entered the Emergency Room of the Hospital das Clínicas da Universidade de São Paulo. Other causes beyond Hepatitis B vaccine, received one month before the hemorrhagic state, were ruled out with the history and laboratory exams. A review of the literature about PTI revealed case reports of the disease connected with Hepatitis B vaccine administration.RESULTS: The vaccine was considered the probable cause. The child was treated with intravenous immunoglobulin, improving from thrombocytopenia after three days, and remaining without symptoms during one month of follow up.CONCLUSION: The thrombocytopenic purpura after hepatitis B vaccine is a rare event whose causal relation is hard to prove. The diagnosis is based on the exclusion of other possible causes, but in this case, the hypothesis may be considered since new cases are being reported in the literature.

The Influence of Labor and Placental Separation on Hemostasis in Term Pregnancy

We studied the hemostatic effects in 68 term preg nant subjects with normal pregnancy (n = 39), gestational diabetes mellitus (n = 21), pregnancy-induced hypertension (n = 8), during labor, after placental separation, and at 24 hours postpartum. During labor, a hypercoagulable state with en hanced fibrinolysis and platelet activation along with elevated plasminogen activator inhibitor-1 and plasminogen activator inhibitor-2 were seen. In all cases following placental separa tion, enhanced fibrinolysis persisted with further elevated tissue plasminogen activator antigen and D-dimer levels, increased thrombin generation and platelet activation with decreasing plasminogen activator inhibitor-1 levels. By 24 hours postpar tum, thrombin generation (thrombin-antithrombin complex) decreased to a nonpregnant level except for pregnancy induced hypertension, but enhanced prothrombin activation (F1+2) was evident in normal, gestational diabetes mellitus and pregnancy- induced hypertension. Reduced total protein S and antithrom bin III activity with normal protein C and elevated fibrinogen levels seen during labor were not affected by delivery. How ever, although factor VII showed a decreasing trend at 24 hours postpartum it remained elevated above the normal nonpregnant level. At 24 hours postpartum, a hypercoagulable state still persisted in normal, gestational diabetes mellitus and preg nancy-induced hypertension term pregnancy accompanied by enhanced fibrinolysis and elevated plasminogen substrate for fibrinolysis, suggesting a critical dynamic equilibrium between a thrombotic and hemorrhagic state.

Molecular Defects in Rare Bleeding Disorders: Hereditary Haemorrhagic Telangiectasia

Vascular diseases may mimic coagulopathies by presenting as a haemorrhagic state. The archetypal example of an inherited disorder resulting in haemorrhage from dilated vessels of the microvasculature (telangiectasia) is Hereditary Haemorrhagic Telangiectasia (HHT, Rendu-Osler-Weber syndrome). This autosomal dominant disorder is characterised by haemorrhage from nasal, mucocutaneous and gastrointestinal telangiectasia, in addition to vascular anomalies in other organs, particularly in the pulmonary, hepatic and cerebral circulations. Linkage analyses have indicated there are at least three HHT loci, including the genes for endoglin on chromosome 9, and activin-like receptor kinase (ALK1) on chromosome 12. Mutations in these genes, together with recent data on the normal function of the encoded proteins highlight the role of TGF-b family members in the pathogenesis of HHT. Complimentary information from other telangiectatic states indicates potential precipitants, and indicate a critical role for TGF-beta ligand-receptor interactions in vascular homeostasis.

Stroke-A Rare Presentation of Eales' Disease A Case Report

Eales' disease is common in India and the Middle East, but its neurologic manifestations are rare. The authors report a young man with recurrent vitreous hemorrhage and acute amnestic confusional state who subsequently developed myelopathy. Eales' disease should be considered in the differential diagnosis of stroke in a young patient.

DDAVP Reduces Bleeding during Continued Hirudin Administration in the Rabbit

Hirudin is a potent thrombin inhibitor derived from the leech Hirudo medicinalis salivary gland which has considerable potential for therapeutic use in thrombotic disease. The major risk attendant its use is hemorrhage. This study investigates the hypothesis that the prohemostatic effects of DDAVP infusion can curtail the hemorrhagic effect induced by ongoing hirudin administration. In a randomized and blinded manner, rabbits were exposed to a 15-min intravenous infusion of DDAVP or saline midway through a continuous two-h intravenous infusion of hirudin. Bleeding time was monitored by full thickness ear punctures performed before, during and after hirudin exposure. Hirudin induced a significant hemorrhagic state, manifest as a 7-10-fold prolongation of the primary bleeding time. DDAVP reduced the mean duration of primary bleeding from 10.8 min to 5.9 min (p = 0.001) as well as the number of sites which bled for longer than 6 or 20 min (46% vs 27%, p = 0.002; and 18% vs 5%, p = 0.002, respectively). Although there was no difference in the incidence of spontaneous rebleeding from these sites (44 vs 36%, p = 0.21), rebleeding did not persist as long in animals that received DDAVP (8 vs 16 min, p = 0.005), and fewer sites rebled for longer than 20 min (8 vs 27%, p = 0.027). Results were essentially the same for two different commercial recombinant hirudin preparations. DDAVP appears to attenuate the bleeding caused by continuous hirudin infusion in rabbits and establishes a foundation for clinical assessment in patients.

Intraoperative coronary artery spasm with hemorrhagic shock state

Intraoperative coronary artery spasm with hemorrhagic shock state

Suprasellar granular-cell tumour, presenting with intraventricular haemorrhage.

A case of suprasellar granular-cell tumour (GCT), presenting with intraventricular haemorrhage is described. The authors emphasize the exceptional character of spontaneous haemorrhage for a GCT, although haemorrhagic state during surgery has often been reported and may hinder total removal. Preoperative arteriography discloses a suprasellar blush in half of the cases. This facilitates the preoperative diagnosis. By taking special preoperative and operative precautions against haemorrhage complete removal can be carried out provided there is no encasement of the optic chiasm.

Intraoperative coronary artery spasm with hemorrhagic shock state

Intraoperative coronary artery spasm with hemorrhagic shock state

Mast cells, vasoactive intestinal peptide (VIP), and the hemorrhagic shock: a possible relationship?

The key mechanisms associated with irreversible hemorrhagic shock have no so far been elucidated. The involvement of mast cells in this phenomenon, however, has already been studied. On the other hand, β-endorphin and various opiates, or any stressful stimuli mediated by endogenous opiates, cause mast cell degranulation and histamine release, as the study of the related literature shows. Hemorrhagic shock is one such stressful stimulus that leads to an increase in the plasma levels of endogenous opioids, especially β-endorphin. During hemorrhagic shock, therefore, mast cells can be activated by an elevation of the β-endorphin level; and the degranulated products of mast cells, histamine in particular, may contribute to the progress of hemorrhagic shock to the irreversible state. The investigation of the effect of hemorrhage on mast cell degranulation has shown that there is a positive correlation between the two phenomena. In addition, it has been established that the administration of vasoactive intestinal peptide (VIP) prevents such degranulation. Depending on these results, the effects of VIP have been studied in the treatment of severe experimental hemorrhagic shock in combination with other therapeutic means used in this type of shock, such as naloxone, hypertonic saline infusion and/or blood reperfusion. A combination of VIP and naloxone has yielded the best results on survival when it is used either alone or in conjunction with volume replacement after a severe hemorrhage. The important prospect of a combination of VIP and naloxone is that it has apparently the most potent inhibitory effect on mast cell degranulation. In the light of the related experiments, we may conclude that the inhibition of mast cell degranulation has a beneficial effect on severe hemorrhagic shock; mast cell degranulation may thus be accepted as a physiopathological mechanisms contributing to the progression of hemorrhagic shock state. Biomedical Reviews 1993; 2: 37-46.

Effect of hemorrhagic hypotension on cerebrovascular reactivity and ultrastructure in the cat.

The goal of this study was to determine the alterations in contractile and dilatory responses and ultrastructure of the feline middle cerebral artery after hemorrhagic hypotension. In the sodium pentobarbital anesthetized cats, a steady 50 mm Hg level of hypotension was reached by bleeding into a reservoir and maintained at this level by further bleeding or autotransfusion for 2 hours. Rings of the arteries, from control animals and from animals after hypotension, were suspended for isometric tension recording in organ chambers filled with modified Krebs-Henseleit solution, aerated with 95% O2-5% CO2 at 37 degrees C, and their reactions to contractile and relaxant agents were tested. Vascular ultrastructure was studied by electron microscope. Endothelium-dependent relaxations induced by 10(-8) M acetylcholine were enhanced, whereas there was a marked inhibition of the relaxation at 10(-6) M. Relaxations induced by adenosine triphosphate and adenosine showed an impairment. Contractions induced by norepinephrine and prostaglandin F2 alpha remained unchanged, whereas 5-hydroxytryptamine caused a more pronounced contraction after hypotension. No alterations in the morphology of endothelium or smooth muscle were found after hemorrhage. There was, however, a marked decrease in the number of transmitter vesicles in the perivascular nerve terminals. The present results show marked alterations in cerebrovascular reactivity and ultrastructure of the adventitia after hypotension. These alterations might play an important role in the development of cerebral vasoconstriction during and after this hemorrhagic state.

Disseminated Intravascular Coagulation: Pathogenesis and Management

Disseminated intravascular coagulation (DIC) is a clini-copathological syndrome secondary to an underlying disease. Characteristic laboratory abnormalities of DIC should suggest, much like the recognition of fever, anemia, or congestive heart failure, that an inciting disease process must be searched for. The clinical and laboratory consequences of DIC can be ascribed to the unregulated and unbalanced formation of thrombin, the main clot-forming enzyme, and plasmin, the main clot-lysing enzyme. If too much plasmin is formed in relation to thrombin, a hemorrhagic state, which appears in 60 to 75% of patients with deep vein thrombosis, will occur. Alternatively, if too much thrombin is formed in relation to the degree of secondary fibrinolysis, a thrombotic condition, which appears in 25 to 40% of patients with DIC, will become manifest. The diagnosis of DIC is dependent on the presence of an appropriate clinical situation with concurrent laboratory evidence of thrombin and plasmin formation. Thrombin formation, plasmin formation, or both, can be assessed by detection of fibrin monomer, fibrin/fibrinogen degradation products, and D-dimer or E fragment, respectively. Treatment of DIC should initially be addressed to treatment of the primary, underlying condition inciting the disorder. If treatment for DIC is specifically needed, blood product replacement is the first order of therapy. This replacement should be tailored to each patient's specific needs (i.e., platelets, fibrinogen, or plasma proteins). Heparin has a definite but limited use in conditions associated with acral cyanosis and dermal ischemia. Other specific therapies for DIC may be of use in individualized situations.

Reduction in thrombus formation by PG-1 F(ab')2, an anti-guinea pig platelet glycoprotein Ib monoclonal antibody.

We have recently demonstrated that intraperitoneal injection into guinea pigs of F(ab')2 fragments of PG-1, a murine monoclonal antibody recognizing the guinea pig homologue of human platelet glycoprotein Ib, produces virtually complete functional block of the platelet von Willebrand factor receptor without inducing a hemorrhagic state. To assess the ability of this antibody to protect against thrombosis resulting from laser-induced injury to mesenteric small arteries, we injected guinea pigs with either PG-1 F(ab')2 (2.3 mg/kg) or with buffer alone 24 hours before study. For each animal, four mesenteric vessels were studied consecutively for 15 minutes each. The number of thrombi, time to first thrombus, and time to embolization of first thrombi were recorded. In the control animals most individual vessels had three to four thrombi, whereas in the antibody-treated animals, vessels most frequently had only a single thrombus or even none at all. The mean number of thrombi per vessel in the antibody-treated animals (1.125) was significantly lower than the mean in the control animals (3.40), with p less than 0.001. However, there was no significant difference between groups with respect to time to first thrombus after laser injury. Detachment of thrombi in the control animals occurred in an easily recordable, discrete fashion, with 75% of first thrombi embolizing in less than 5 minutes. In the antibody-treated animals, gradual dissolution rather than discrete detachment was typically observed. In 31% of the vessels studied in these animals, no embolus occurred; for the remaining vessels only 9% of thrombi were observed to embolize within 5 minutes of their formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Very Low Doses of Warfarin Can Prevent Thrombosis in Central Venous Catheters

To determine whether very low doses of warfarin are useful in thrombosis prophylaxis in patients with central venous catheters. Patients at risk for thrombosis associated with chronic indwelling central venous catheters were prospectively and randomly assigned to receive or not to receive 1 mg of warfarin, beginning 3 days before catheter insertion and continuing for 90 days. Subclavian, innominate, and superior vena cava venograms were done at onset of thrombosis symptoms or after 90 days in the study. One hundred twenty-one patients entered the study, and 82 patients completed the study. Of 42 patients completing the study while receiving warfarin, 4 had venogram-proven thrombosis. All 4 had symptoms from thrombosis. Of 40 patients completing the study while not receiving warfarin, 15 had venogram-proven thrombosis, and 10 had symptoms from thrombosis (P less than 0.001). There were no measurable changes in the coagulation values assayed due to this warfarin dose, except in occasional patients who had become anorectic because of their disease or chemotherapy. Very low doses of warfarin can protect against thrombosis without inducing a hemorrhagic state. This approach may be applicable to other groups of patients.