[Hemostasis through infrared irradiation. A new and simple method for hemostasis of parenchymatous tissues].
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This discussion has outlined several simple and reliable test systems which have been found useful in assessing disorders of hemostasis in the hemorrhaging CPB patient. When these tests are utilized as described in the preceding article, they have been extremely helpful in studying hemostasis in the CPB patient to be reexplored; they are equally helpful to quickly render a differential diagnosis of altered hemostasis when hemorrhage occurs. In addition, several "special" procedures, the AT-III and heparin assays, have been reviewed; these have been found quite useful in special instances of CPB hemorrhage, and community cardiovascular teams may wish them to be available. This paper has not presumed to be "authoritative" with respect to the "best" tests for assessing CPB hemostasis, but rather has offered only an approach helpful to the authors. The intent has, however, been to provide guidelines for instituting simple, reliable, and workable procedures for the community hospital where CPB is now routinely performed.
Heparinized porcine blood and plasma, at constant hydrostatic pressure, was allowed to flow through a 5-mm incision in a small piece of porcine skin. Changes in the exuded blood volume were measured, and the incision site was examined microscopically. When normal blood flowed through either normal or von Willebrand skin, the exuded blood volume decreased gradually and eventually stopped. Microscopic examination revealed a platelet plug in the incision site. This plug was positive for Willebrand factor when examined by immunofluorescence. In contrast, the blood from von Willebrand pigs continued to flow constantly, and a platelet plug was not seen. The delayed in vitro hemostasis in von Willebrand blood was corrected to the normal range by the addition of either normal plasma or partially purified Willebrand factor. Normal blood, in which the Willebrand factor was immunologically inhibited, showed delayed hemostasis. For this in vitro system, it appeared that plasmatic Willebrand factor played an essential role in hemostasis.
In a retrospective study the results of laboratory investigations were correlated with actual or previous bleeding symptoms of 40 patients. In 22 patients, a defect of hemostasis was documented in the laboratory, whereas the bleeding disorder, suggested by severe hemorrhage, could not be classified in 3 additional patients. In the remaining 15 individuals, no abnormality could be detected by the available laboratory methods. In the group with a documented bleeding disorder, 13 of 22 patients had prolonged bleeding following dental extraction or other surgery of the oral cavity. Other bleeding symptoms were equally distributed among patients with and without a documented defect. 3 patients had a positive family history, i.e. relatives with a hemorrhagic tendency. In 6 patients, a correlation between bleeding and the ingestion of acetylsalicylic acid could be established, while in 4 it was probable. Hemorrhagic complications following oral surgery, particularly in combination with drugs known to interfere with platelet function and a positive family history, strongly suggest an abnormality of hemostasis. Among the 22 patients with a documented defect of hemostasis, only 6 were found who did not present at least one of these leading symptoms.
From the beginning of the millennium and the development of genome-wide analyses, the technical advances and remarkable increase in research sample sizes have led to an escalating number of discoveries revealing genetic determinants of levels of the main factors regulating hemostasis and thrombosis and demonstrating a clear polygenic complex regulation of most coagulation factors. These discoveries have been useful to understand the biology underlying hemostasis regulation and to understand risk of associated thrombotic disease, such as venous thromboembolism, coronary artery disease, and ischemic stroke. In this historical review, we outline the main discoveries in genetic studies of coagulation factors (fibrinogen and its alternatively spliced γ' isoform, D-dimer, factor [F]V, FVII, FVIII, von Willebrand factor, and FXI), the main natural anticoagulants (protein C, protein S, and antithrombin), components of fibrinolysis (tissue plasminogen activator and plasminogen activator inhibitor-1), and global coagulation tests (prothrombin time and activated partial thromboplastin time). We explore the clinical implications of these discoveries and suggest new avenues for future investigation.
Disorders of hemostasis are frequent in malignant disease and their cause is often multifactorial and complex. Both primary (platelets and vessel walls) and secondary (coagulation factors) hemostasis are impaired, often concurrently. Therapy is most often directed toward the underlying disease; however, a knowledge of the complications and treatment of each malignancy will often prevent a number of the problems cited in this chapter. The hypercoagulable states are still poorly understood and need better definition, but their recognition, treatment and prevention may decrease morbidity significantly.
Seven patients with classic hemophilia A had alteration of primary hemostasis after treatment with lyophilized antihemophilic globulin (LAHG). The following test results, which were normal before treatment, became abnormal after treatment: bleeding time, bleeding intensity, and platelet adhesiveness. In two patients, the fibrin-fibrinogen-degradation products increased to more than 40 microgram/ml. In three patients, the bleeding symptoms became worse with LAHG therapy although no inhibitor against Factor VIII was demonstrated. In one of these patients, the bleedings symptoms disappeared when the use of LAHG was discontinued and prednisone was given; at the same time, the altered primary hemostasis returned to normal. In the remaining two patients, prednisone did not have any effect. In these two patients, however, the bleeding stopped, and the bleeding time became normal immediately after freshly prepared blood-group compatible cryoprecipitate was given.
An intravesicoprostatic hydrostatic pressure below 10 mm Hg maintains normal anatomy and physiology of the muscular and vascular prostatic structures by continuous pump suction. An increase of the hydrostatic intravesicoprostatic pressure above 10 mm Hg produces a distortion in the musculature of the prostate, especially at the true capsule, opening the cut vessels, making possible the absorption of the irrigant free of electrolytes (TUR syndrome). A low hydrostatic intravesicoprostatic pressure permits the compression of cut vessels by the inflow hydraulic pressure of 90 cm H2O achieving hydraulic hemostasis during TURP reducing the bleeding and operative time by more than 50% and making hemostasis easier. In our last 400 TURs, blood transfusions have been unnecessary. Less electrocoagulation is required, resulting in a more rapid recovery.
The indices of microcirculatory hemostasis were studied in 955 persons, 200 of whom were healthy while 755 had diseases of the heart and vessels. The results were compared with blood fibrinolytic and coagulation activity and with the functional condition of the basophil-mast cell apparatus. A reverse trend in the functional shifts of microcirculatory and plasmo-coagulative hemostasis in the reaction of emergency adaptation was established. Delayed formation and increased resistance of platelet aggregates with simultaneous decrease in the number of platelets in circulation were revealed in cardiovascular diseases during a remission, which reflects intensified expenditure of the platelets or their aggregation energy in the microcirculatory channel. The administration of exogenous heparin, just like the period of basophil degranulation in stresses of various origin, is attended with distinct platelet hyperfunction which allows small doses of heparin to be used for the prevention of diapedetic hemorrhages in hypertensive disease.
High molecular weight (approximately 60,000) dextran having been selected in a protocol of per-operative hemodilution, a prior study was undertaken in vitro in order to measure the variations in parameters of hemostasis. Factor of primary hemostasis, of plasma coagulation and fibrinolysis were thus evaluated in control blood samples, not diluted and diluted to 1/5 th by dextran or by a buffer solution. Statistical analysis was carried out using the t-test for pairs of variables. The following emerge from the results: 1 - an absence of difference with regard to the fibrinolytic activity of the plasma, but marked fragility of the fibrin clot in the presence of dextran; 2 - variations for plasma coagulation factors due to dilution; 3 - acceleration of the phase of polymerisation of fibrin monomeres and a decrease in platelet stickiness and aggregation due to dextran.
A microcystalline collagen hemostat effected rapid hemostasis in dental extractions for a hemophilic patient with a significant level of inhibitor where preoperative transfusion of deficient factor was contraindicated. It appears that MCH can be used safely and effectively for a variety of oral procedures. In addition to its hemostatic properties, the ease with which it can be handled and its adherence make it adaptable for use in locations of limited access. In comparison with currently used materials, such as gelatin foam, it may have wider application and may be of greater benefit in achieving hemostasis in procedures in the oral cavity.
Hemostatic plug formation has been studied in the rabbit mesenteric microcirculation during normovolemic hemodilution. A hemodilution method has been developed which maintains a constant platelet count. Using this method the primary hemostatic plug formation time (PHT) and the total hemostatic plug formation time (THT) has been assessed for different degrees of hemodilutions. Both PHT and THT are significantly prolonged for arterioles perfused with low hematocrits (10.6 and 14.2). At a hematocrit of 19.0 the hemostasis is most effective with the shortest hemostatic plug formation times.
Glanzmann's thromboasthenia is a rare congenital platelet disorder characterized by a prolonged bleeding time, a qualitative platelet defect, and severe hemorrhagic episodes. Patients with this disorder have been managed by administration of blood and blood components (most recently, platelet-rich plasma and platelet concentrates) to control hemorrhage resulting from trauma or surgical procedures. The two case reports presented here illustrate the use of a local hemostatic agent (microfibrillar bovine collagen, Avitene) and a systemic fibrinolytic inhibitor (epsilon aminocaproic acid, Amicar) to control postoperative hemorrhage secondary to elective extraction of teeth. The clinical results demonstrate excellent postoperative hemostasis and support recent in vitro observation of platelet adherence to the collagen preparation. This provides an alternate therapeutic modality in the management of patients with Glanzmann's disease and possibly other disorders of platelet function.
Twenty-seven patients requiring massive transfusions were studied prospectively to determine whether administration of stored, modified whole blood induced a primary disorder of hemostasis evidenced by generalized microvascular oozing. Platelet counts fell in proportion to the number of units of blood transfused. In contrast, the levels of factors V and VIII correlated poorly with the units of blood transfused, 85% of the total variation in the levels being due to influences other than transfused blood. Levels of all other clotting factors were unrelated to the number of units of blood given. Eight patients developed abnormal bleeding. The cause appeared to be dilutional thrombocytopenia in five patients, and DIC in three. In six of the eight, bleeding was controlled with platelet concentrates alone. Two patients were given cryoprecipitate also. The most useful laboratory test for predicting abnormal bleeding was the platelet count. Fibrinogen levels should be followed as an aid in the diagnosis of DIC. The BT, PT, and PTT were not helpful in assessing the cause of bleeding, unless they were greater than 1.5 times the control value. We recommend that any patient receiving massive transfusions who develops diffuse microvascular bleeding be given platelet concentrates. Platelet counts as high as 100,000 may be required to control bleeding from surgical wounds. It is not necessary to supplement transfusions of stored, modified whole blood with fresh blood or fresh frozen plasma.
Effects on hemostasis of deep hypothermia on infant has been studied on 29 infants operated upon for a cardiopathy under deep hypothermia. Results of this study show a diminution of the coagulation factors rate, an augmentation of the fibrinolytic activity and an unforeseable variability of the residual heparin leading in all cases to a complement of the heparin neutralization by Protamine.
The effects of aspirin and acetaminophen on postextraction hemostasis were evaluated in a double-blind study in a group of 43 patients; 20 received aspirin and 23 received acetaminophen. No significant difference was found in the observed postsurgical alveolus bleeding times or the patients' reported length of postoperative bleeding. However, Ivy bleeding times taken after the ingestion of 80 grains of medication showed an elevation in 75% of the aspirin users and in 60% of the acetaminophen group; the mean change in bleeding times was 2.75 times greater in the aspirin group.
The in vivo formation of hemostatic plugs was studied in humans in skin wounds made using the template bleeding procedure of Mielke (34). The wounds were excised by punch biopsy 10 seconds, 30 seconds, 2 minutes, and 3 minutes after they were made. The wounds were V-shaped and approximately 0.4 mm. deep. Within 30 seconds small hemostatic plugs were observed at the end of transected vessels. The plugs grew in size in the subsequent minutes and became impermeable. The platelets degranulated and formed pseudopods which became strongly interdigitated. The platelets at the periphery of the plugs showed discontinuities of the membranes. Cytoplasmic matrix and cell organelles had disappeared in many of these peripheral cells. Small fibrin fibers were already found at 30 seconds, mostly along the margins of the wounds and also at the periphery of the hemostatic plugs. Fibrin was absent from the center of the plugs and from the lumen of transected vessels. When part of a plug was extending into the vessel lumen, the platelets inside the vessel were less degranulated and less interdigitated than the rest of the plug. The effect of acetysalicylic acid (ASA) was studied in wounds before and 2.5 hours after ingestion of 2 gm. of ASA. Wounds were excised by punch biopsy 3 or 10 minutes after they had been made. Platelets in ASA were less degranulated, had fewer pseudopods, and showed less interdigitation than platelets in control plugs. Ballooning and fibrin deposition were similar in control and ASA plugs. Pronounced differences between control and ASA plugs were observed in a subject who exhibited a considerably prolonged bleeding time after ASA. The ASA plugs were very large; many plugs had fused and in addition numerous small platelet clumps, most likely fragments from the plugs, were found in the superficial scab of the wound. It is postulated that ASA plugs are less stable due to decreased interdigitation. This allows more disruption of the plugs and rebleeding. Consequently, more platelets are needed and longer time is required for hemostasis to occur.