Disseminated Intravascular Coagulation - Assignment Example

Case Study: To Carry Out Haematological, Biochemical and Microbiological Investigations for the Case Study Below and Give Possible Provisional Diagnosis. Introduction: This case study is about a young patient who sustained severe road traffic accident that led to multiple fractures in different locations in the body and major visceral injuries. From the history, it is evident that this patient had to be given multiple units of blood and blood products to resuscitate him and for replenishment of the loss that occurred due to surgeries in his liver and spleen. Following this, the patient developed clinical signs of coagulopathy as evidenced by haematuria, bleeding at the line attachments, and appearance of petechaeal rashes as noted by the nurse. Even though he was registering a good recovery following his multi-organ surgery in the lungs, kidneys, liver and splenectomy in the high-dependency unit, from the sixth postoperative day, he began to deteriorate, and this called for investigations about the possible aetiology of his sudden deterioration despite initial evidence of recovery. The potential risk factors for his deterioration are multiple bony traumas; multi-organ injuries and surgeries including lungs, liver, kidneys, and spleen; multiple blood transfusions; and hospital-acquired infection in the high-dependency unit. The provisional diagnosis could be one of acquired coagulopathy that may have resulted due to the above risk factors. The provisional diagnosis could be DIC or disseminated intravascular coagulation since the most common signs of this disorder are petechiae, ecchymosis, and oozing from venipuncture sites and catheter sites, as well as bleeding from surgical incisions (Attar et al., 1969, p. 939-965). In some situations, DIC becomes only evident after laboratory analysis with mild or no clinical symptoms at all. As in this case, these patients become symptomatic after stress situations, such as, surgery, or severe infections. The common denominator of DIC is the pathological generation of thrombin, which leads to widespread intravascular deposition of fibrin and to the consumption of coagulation factors and platelets. DIC is as such not a disease entity, but the consequence of a variety of disorders that diffusely lead to the activation of coagulation mechanisms within the bloodstream (Carey and Rodgers, 1998, 65-73). The formation of thrombi in the microcirculation activates the fibrinolytic process as a compensatory mechanism to lyse the clots. This mechanism generates circulating fibrin degradation products, which in concert with the coagulation deficiencies and thrombocytopenia results in bleeding. DIC occurs in a wide spectrum of diseases. Another mechanism potentially triggering DIC is the widespread endothelial damage occurring in endotoxinaemia, meningococcal septicemia, or following severe burns or hypothermia. Vascular stasis as in circulatory shock and severe pulmonary embolism can also precipitate DIC (Hack and Zeerleder, 2001, s21-s27). In this patient, this has been an acquired coagulation disorder. The acquired forms usually are associated with multiple coagulation abnormalities, and the disorder often is complicated by thrombocytopenia, deficient platelet function, abnormal inhibitors of coagulation, and vascular abnormalities. Because of the compound nature of the haemostatic defect, the severity of bleeding often correlates poorly with the results of laboratory tests in patients with acquired coagulation disorders, and replacement therapy may be ineffective. The clinical picture is often complicated by signs and symptoms of the underlying disease. In this patient, there is a chance for septicemia due to the facts that the patient had a road traffic accident, had massive trauma, multiple surgeries, and the patient had been put in an intensive care unit. Major risk factors of gram-positive bacteriaemia include vascular catheterization and the presence of indwelling devices. Mechanical ventilation has also a role to play (Baglin T., 1996, p 683-687). The septic response is usually triggered when microorganisms spread from the GI tract or skin into the contiguous tissues. Microorganisms may also be introduced directly into the blood stream via intravenous catheters. In a minority of cases, no apparent source of infection is apparent. In general, the septic response occurs when an invading organism has circumvented the host’s innate and acquired immune response. Sepsis may be a cause precipitating disseminated intravascular coagulation in this patient. Intravascular fibrin deposition, thrombosis, and DIC are important features of the septic response. TNFα promotes intravascular coagulation initially by inducing blood monocytes to express tissue factor. When tissue factor is expressed on monocytes, it binds to factors VIIa to form an active complex that can convert factors X and IX to enzymatically active forms. The result is activation of both intrinsic and extrinsic pathways for clotting (McGrath and Stewart, 1969, p. 833-848).. This culminates into generation of fibrin. Thus there is a striking propensity for intravascular fibrin deposition, thrombosis, and bleeding. In most severe infections, the complicating influence of septic shock may be considerable. It has been suggested that DIC is involved in all forms of shock and that it is the central feature in irreversible or refractory forms. In septic shock, the interrelationships between septicemia, shock, and endotoxaemia are exceedingly complex. In septicemia, both thrombocytopenia and septic shock may occur without DIC. Shock may favor the development of DIC by potentiating various activating stimuli that ordinarily would not exceed the capacity of compensatory processes and may perpetuate DIC after a transient activating stimulus has been dissipated (Ginkel et al., 1977, 35-45). Hypoperfusion, even of normal vessels, acidosis, and hypoxemia produce hypercoagulability and favor intravascular platelet aggregation. DIC constitutes a model of accelerated turnover of various coagulation factors, the levels of which at any time are determined by the size of the plasma pool and the differences between the rates at which they are being destroyed and replenished. In this patient, the depletion of plasma fibrinogen has induced a compensatory release of large amounts of fibrinogen into the circulation, possibly from the hepatic-lymphatic system, and also has increased the rate of fibrinogen synthesis (McKay DG., 1969, p.646-660). Activation of vascular endothelium also might have played a major role in the pathogenesis in this patient. Tissue damage due to trauma and surgery had been the initiating event in this patient. Associated sepsis also has added to the baseline tissue damage. The probable underlying mechanism is widespread vascular endothelial injury with fluid extravasations and microthrombosis that had decreased oxygen and substrate utilization by the affected tissues. Leukocyte derived mediators and platelet, leukocyte, fibrin thrombi would have added to this injury already present. Endothelial cell activation has important role to play to attract phagocytes to the site of injury, but the most significant role that may play in this particular patient is promotion of vascular permeability, microvascular thrombosis, DIC, and hypotension. As has been highlighted earlier massive trauma, bacterial sepsis, and consumption coagulopathy are very important predisposing causes that could have led to DIC in this patient. The pathophysiology of DIC is complex. The mechanisms that activate or “trigger” DIC act on processes that are involved in normal haemostasis, the processes of platelet adhesion and aggregation and contact-activated and tissue factor–activated pathways of coagulation. These mechanisms exceed the normal compensatory process. Thrombin is persistently generated, and fibrin is formed in the circulating blood. Fibrinogen, various other coagulation factors, and platelets are consumed. The fibrinolytic mechanism is activated, and large amounts of FDP are produced, which further impair haemostatic function van (Ginkel et al., 1977, 35-45). Bleeding, shock, and vascular occlusion commonly supervene and produce profound alterations in the function of various organ systems. Normal compensatory processes become impaired. The ultimate outcome is determined by a dynamic interplay between fibrin deposition versus fibrinolysis; depletion versus repletion of coagulation factors and platelets; and production versus clearance of fibrin, FDPs, and other products of coagulation. Like in this patient, in most forms of DIC, the initiating factors are multiple and interrelated. In DIC associated with massive trauma, major surgical procedures, additional abnormalities and complications are important contributory factors. In this case, particularly, “hypercoagulability,” azotemia, shock, intravascular hemolysis, massive transfusions of stored blood, septicemia, and hypoxia, all might have contributed to the development of the disorder. The vascular endothelial inflammatory response and the effects of endotoxin in general are highly species-specific, and DIC may complicate acute infections involving bacteria that lack potent endotoxins—for example, pneumococci, which produce DIC most often in asplenic individuals. This patient has been rendered asplenic by splenectomy. Therefore, he might be having a pneumococcal sepsis. In pneumococcal sepsis, intact pneumococci, their polysaccharide capsular antigens, or antigen-antibody complexes formed there might have triggered coagulation by interacting with the complement system (Harker and Slichter, 1972, p. 999-1005). With this pathophysiologic background, the battery of laboratory investigations that were undertaken in this patient was many. The complete blood count showed low haemoglobin at 8.0 g/dL, platelet count was decreased below the lower normal range at 56 x 109/L, and leukocyte count was high at 16 x 109/L. These indicated the patient is anemic and having effects of blood loss. The coagulopathy is a consumption coagulopathy indicated by very, very low platelet count, and massive sepsis indicated by very high white cell count. The blood film examination showed N79, L10, M5, E5, B1, and NRBC occasional indicating sepsis response and evidence of continued blood loss. RBC morphology showed noticeable poikilocytes, polychromatic cells very high, and schstiocytes. In patients with DIC, routine hematologic tests may reveal evidence of acute bleeding, accelerated red cell destruction, or signs of the underlying disease. Examination of the blood smear reveals schistocytes in approximately 50% of cases, but the degree of schistocytosis bears no necessary correlation with other facets of the disorder (Visudhiphan, Piankijagum, Sathayapraseart, Mitrchai, 1983, p. 113). Thrombocytopenia is an early and consistent sign of acute DIC, and the consideration of this diagnosis in the presence of a persistently normal platelet count is difficult. Platelet counts in the range of 50,000 to 100,000/dl are the usual finding, but thrombocytopenia may be severe. The coagulation screen was vividly abnormal, and in this patient PT, aPTT, and TT, all increased far beyond the normal level, indicating serious coagulopathy. The PTT, PT, and thrombin time are prolonged in most patients with acute DIC. The plasma levels of fibrinogen and of factors V and XIII usually are significantly depressed; fibrinogen and factor V are the most consistently affected. The level of factor X may be lower than that of other “stable” factors VII, IX, and XI, which usually are present in normal amounts (Okajima, Sakamoto, Uchiba, 2000, p. 215-222). Clinical microbiology has revealed gram-negative sepsis sensitive to ciprofloxacin, gentamicin, and nitrofurantoin, and resistant to ampicillin, chloramphenicol, and trimethoprim. This is a nonhemolytic bacteria and indole and oxidase negative, and therefore lacking significant virulence factor. With appropriate antibiotic therapy, this infection can be controlled. In light of this patient history, ventilator assisted care could be the reason, and the source might be hospital acquired. Therefore containment of the bacteria is an important step to prevent spread. The combination of ciprofloxacin and genetamicin could be the antibiotic of choice in his treatment (Spero, Lewis, Hasiba, 1980, 28-33). Although the patient had low urea at the consent of 10 mmol/L, the sodium was very low at 129 mmol/L indicating hyponatraemia. This could have happened due to haemodilution as a result of fluid replenishment. However, the potassium was at the high normal range indicating hyperkalaemia that could have been due to massive blood transfusion, tissue injury, and renal failure indicated by creatinine clearance. This patient needs renal support and treatment of azotaemia. The plasma fibrinogen level, PTT, PT, platelet count, and estimates of FDP or D-dimer are the cornerstones on which the diagnosis of DIC is based. These simple tests should always be performed first. Additional information may confirm, but seldom refutes, the diagnosis of DIC if typical abnormalities are demonstrated by these tests. Laboratory data may change with remarkable rapidity in DIC, based on disease progression or therapy. The best test for diagnosing DIC is the D-dimer assay. The semiquantitative method is sensitive, and D-dimer values greater than 2000 ng/mL have been reported to be consistent with DIC (Siegal, Seligsohn, Aghai, Modan, 1978, p. 122-134). More sensitive, quantitative D-dimer assays are available, but DIC diagnostic ranges are not yet defined for this latter method. A new test, measurement of the biphasic waveform in the PTT assay, has been reported to precede development of DIC and to predict DIC better than the D-dimer assay. In most patients with DIC, FDP levels as determined by quantitative methods, such as red cell hemagglutination inhibition or latex agglutination. Fibrinopeptide A and certain fibrinogen fragments that are formed by the lysis of cross-linked fibrin, such as the DD-dimer and the DD-dimer–E complex, can be demonstrated by using special techniques (Carr, McKinney, McDonagh, 1989, p. 280-287). These latter FDPs provide direct evidence of the action of thrombin on fibrinogen and provide a means of differentiating fibrin degradation products from fibrinogen degradation products. Plasma levels of fibrinopeptide A and the rate of incorporation of 14C-labeled glycine ethyl ester into soluble “circulating fibrin” are exceptionally sensitive indicators of DIC and may be abnormal even in patients with normal levels of FDP. Levels of antithrombin, a 2-antiplasmin, and proteins C and S may be diminished in some cases. Other parameters of activation of coagulation and fibrinolysis have been studied in DIC, especially in sepsis. Thrombin–antithrombin III (TAT) complexes and plasmin–a 2-antiplasmin (PAP) complexes are often elevated in sepsis-associated DIC. Assays such as TAT and PAP complexes may have prognostic significance in DIC, as may other coagulation parameters, including plasminogen activator inhibitor type-1, vWF antigen, and a 2-antiplasmin (Carey, Rodgers, 1998, p. 65-73). Conclusion: The provisional diagnosis of this unfortunate man is disseminated intravascular coagulation as is evidenced by the study above. Although the various reasons for this seemingly catastrophic disorder has been identified in this case, the prognosis is very poor despite aggressive management. References Attar S, Boyd D, Layne E, et al., 1969. Alterations in coagulation and fibrinolytic mechanisms in acute trauma. J Trauma;9:939–965. Baglin T., 1996. Disseminated intravascular coagulation: diagnosis and treatment. BMJ;312:683–687. Carey MJ, Rodgers GM., 1998. Disseminated intravascular coagulation: clinical and laboratory aspects. Am J Hematol; 59:65–73. Carr JM, McKinney M, McDonagh J., 1989 Diagnosis of disseminated intravascular coagulation. Role of D-dimer. Am J Clin Pathol; 91:280–287. Hack CE, Zeerleder S., 2001. The endothelium in sepsis: source of and a target for inflammation. Crit Care Med;29:S21–27. Harker LA, Slichter SJ., 1972. Platelet and fibrinogen consumption in man. N Engl J Med;287:999–1005. McGrath JM, Stewart GJ., 1969. The effects of endotoxin on vascular endothelium. J Exp Med;129:833–848. McKay DG., 1969. Trauma and disseminated intravascular coagulation. J Trauma;9:646–660. Okajima K, Sakamoto Y, Uchiba M., 2000. Heterogeneity in the incidence and clinical manifestations of disseminated intravascular coagulation: a study of 204 cases. Am J Hematol; 65: 215–222. Spero JA, Lewis JH, Hasiba U., 1980. Disseminated intravascular coagulation. Findings in 346 patients. Thromb Haemost;43:28–33. Siegal T, Seligsohn U, Aghai E, Modan M., 1978. Clinical and laboratory aspects of disseminated intravascular coagulation (DIC): a study of 118 cases. Thromb Haemost;39:122–134. van Ginkel CJ, van Aken WG, Oh JI, Vreeken J., 1977. Stimulation of monocyte procoagulant activity by adherence to different surfaces. Br J Haematol;37:35–45. Visudhiphan S, Piankijagum A, Sathayapraseart P, Mitrchai N., 1983. Erythrocyte fragmentation in disseminated intravascular coagulation and other diseases. N Engl J Med;309:113. Read More