Journal of Postgraduate Medicine
 Open access journal indexed with Index Medicus & ISI's SCI  
Users online: 15591  
Home | Subscribe | Feedback | Login 
About Latest Articles Back-Issues Articlesmenu-bullet Search Instructions Online Submission Subscribe Etcetera Contact
 :: Next article
 :: Previous article 
 :: Table of Contents
 ::  Similar in PUBMED
 ::  Search Pubmed for
 ::  Search in Google Scholar for
 ::Related articles
 ::  Article in PDF (44 KB)
 ::  Citation Manager
 ::  Access Statistics
 ::  Reader Comments
 ::  Email Alert *
 ::  Add to My List *
* Registration required (free) 

  IN THIS Article
 ::  Normal coagulation
 ::  Pathogenesis of ...
 ::  Etiology
 ::  Clinical features
 ::  Laboratory inves...
 ::  Diagnosis
 ::  Treatment
 ::  Prognosis
 ::  Acknowledgment
 ::  References
 ::  Article Figures
 ::  Article Tables

 Article Access Statistics
    PDF Downloaded325    
    Comments [Add]    

Recommend this journal


Year : 1992  |  Volume : 38  |  Issue : 4  |  Page : 186-93

Disseminated intravascular coagulation: a review with experience from an intensive care unit in India.

Dept of Medicine, KEM Hospital, Parel, Bombay, Maharashtra.

Correspondence Address:
D R Karnad
Dept of Medicine, KEM Hospital, Parel, Bombay, Maharashtra.

Login to access the Email id

Source of Support: None, Conflict of Interest: None

PMID: 0001307591

Rights and PermissionsRights and Permissions

Keywords: Blood Coagulation, physiology,Causality, Disseminated Intravascular Coagulation, blood,diagnosis,epidemiology,etiology,therapy,Human, India, Intensive Care Units, Prognosis,

How to cite this article:
Karnad D R, Vasani J. Disseminated intravascular coagulation: a review with experience from an intensive care unit in India. J Postgrad Med 1992;38:186

How to cite this URL:
Karnad D R, Vasani J. Disseminated intravascular coagulation: a review with experience from an intensive care unit in India. J Postgrad Med [serial online] 1992 [cited 2023 Mar 24];38:186. Available from:

Disseminated intravascular coagulation is a unique disorder, which is almost never primary, but can complicate a variety of other diseases[1]. It is a collection of paradoxes: it results from a complex interplay of excessive activation of the clotting cascade as well as the fibrinolytic system leading to potentially fatal microvascular thrombosis together with a tendency to bleed excessively. The choice of treatment varies rom replacement of clotting factors to use of anticoagul nts and antifibrinolytic drugs. As the management has to be tailored for a particular patient depending on the clinical picture, a clear understanding of the underlying processes in in order.

  ::   Normal coagulation Top

The coagulation cascade consists of plasma proteins, which are pro-enzymes. Activation of one factor leads to sequential activation of others, culminating in the formation of a fibrin clot[2]. Intital activation may occur via the intrinsic pathway when blood comes in contact with negatively charged surfaces like subendothelial collagen, or by the extrinsic pathway when blood comes in contact with tissue thromboplastin, a lipoprotein. Both pathways ultimately lead to activation of factor X, which converts prothrombin to thrombin, which in turn acts on fibrinogen to form fibrin[2],[3],[4].

An essential feature of the coagulation cascade is amplification of factor activation at each step, which could theoretically lead to production of large quantities of thrombin[3],[4]. Moreover, these factors must be inactivated after they have served their function. Circulating antithrombotic plasma proteins antithrombin Ill, protein C and protein S serve this function. Antithrombin Ill (heparin cofactor) binds to heparin sulphate on endothelial cell membranes and inhibits action of thrombin and activated factors X, IX and Xl[5],[6]. Activated protein C cleaves factors V and VIII. It is activated by thrombin in the presence of thrombomodulin, which is located on endothelial membranes. Protein S serves as a cofactor in this reaction. Protein C also activates the fibrinolytic system. Thus, these proteins have therefore also been called suicide proteins"[6].

Once the breach in the vessel wall has been sealed by a fibrin clot and healing takes place, the clot becomes an impediment to circulation. The insoluble fibrin is then removed by the fibrinolytic system[2],[3]. The plasma protein plasminogen on activation forms plasmin, which breaks down fibrin as well as intact fibrinogen into fibrin/fibrinogen degradation products (FDP). Like prothrombin in the clotting cascade, plasminogen too is activated by intrinsic and extrinsic pathways[2]. The stimuli which initiate clotting, invariably activate fibrinolysis too. In fact, a close parallel can be drawn between the coagulation and the fibrinolytic processes (See [Figure - 1]). Thus, fibrinolysis is inseperably linked to the coagulation cascade[7].

  ::   Pathogenesis of disseminated intravascular coagulation Top

DIC results when there is an inappropriate widespread activation of the coagulation cascade[1],[8],[9],[10],[11],[12],[13]. Once activated, extensive intravascular coagulation should be expected. However, this is often not clinically evident, because the antithrombotic proteins rapidly degrade activated clotting factors [8],[9]. Moreover, as fibrinolysis parallels coagulation, fibrin formed is rapidly degraded into FDP[8],[9],[10],[11],[12]. The net result is a depletion of clotting factors due to activation, degradation and fibrinolysis, resulting in a haemorrhagic diathesis. In addition to its action on fibrin, plasmin also acts on intact fibrinogen producing soluble degradation roducts, many of which possess anticoagulant activity?[7],[11],[12].

Thrombin is a potent stimulus for platelet aggregation and degranulation[14]. Sometimes, the initiating event may also directly activate platelets[11],[12],[15],[16]. Thus, platelets too, are recruited in the intravascular coagulopathy. By providing platelet factor 3 and also a cellular lipid surface, platelets greatly accelerate the coagulation process[8],[9],[12]. Furthermore, the platelets which remain in circulation are defective in their haemostatic function probably due to prior degranulation by thrombin[9],[17]. Thus, thrombocytopenia and the platelet dysfunction further worsen the coagulopathy[9].

Antithrombin III and Protein C form complexes with activated clotting factors and initially tend to control the intravascular coagulation. They are soon depleted allowing the coagulation to proceed unbridled[18],[19]. Deposition of platelets and fibrin along vascular walls results in traumatic hemolysis of red blood cells[20] liberating stromal components, which can by themselves initiate DIC[21]. Finally, ischaemic organ damage, acidosis, hypotension, anoxia and tissue inflammation can add to the procoagulant process by activating clotting factors[11],[12].

Cells of the reticuloendothelial system normally phagocytose circulating activated clotting factors[21],[22]. The protein fibronectin aids in this by opsonizing activated clotting factors [23]. Plasma fibronectin levels are low in DIC presumably due to consumption[23],[24]. Besides, reticuloendothekal cell function is suppressed by compounds like bacterial endotoxin or thrombin[11],[12]. The half-life of activated clotting factors is therefore greatly prolonged, adding to intravascular coagulation[23].

  ::   Etiology Top

A variety of stimuli may initiate DIC by activating the intrinsic or extrinsic pathways or by direct action on fibrinogen. Some conditions like liver disease, speticaemia and fat embolism may activate more than one mechanism. The extrinsic pathway is activated by tissue thromboplastin release in patients with crush injuries, head injury, fat embolism, abruptio placentae and a retained dead foetus[7],[8],[11]. Thromboplastin-like material is implicated in the sepsis syndrome, intravascular haemolysis, aminotic fluid embolism, acute promyeloctic leukernia and mucinous adenocarcinoma[11],[12]. Endothelial damage can activate the intrinsic pathway in Jmmune complex mediated vasculitis, purpura fulminans, rickettsial fever, acidosis, sepsis syndrome, anoxia, heat stroke and burns[1],[11],[15],[16]. Direct activation of factor by fibrinogen occurs in snake bite, pancreatitis, liver disease and fat embolism[7].

In developed countries, infections are the commonest cause of DIC, followed by malignancy[25],[26]. In our country, obstetric conditions are the commonest, followed by infections and snakebite [Table - 1]. This is probably a reflection of the large proportion of pregnant women who do not seek antenatal medical attention[27].

  ::   Clinical features Top

Factors which influence the clinical course of DIC include potency of the procoagulant agent and its dose, the speed with which this enters the body (as in amniotic fluid embolism), presence of coexisting enclothelial damage (e.g. Rocky Mountain spotted fever), vasomotor changes (e.g. DIC due to endotoxin shock) and the state of the reticuloendthelial system[1]. It may thus present as an acute or chronic disorder.

Acute DIC: This presents with life-threatening bleeding from various sites, often in a patient who is already seriously ill[8],[9],[26]. Shock and multiple organ failure frequently coexist[27], making therapeutic decisions difficult. It can exist in the compensated and uncompensated forms[28].

Compensated DIC: When the stimulus for coagulation is mild, the liver can increase production of clotting factors to up to 5 times the normal rate, 'in an effort to maintain plasma levels[29]. Similarly, 2 platelet production too can increase up to 10 times[9]. Thus, although coagulation and fibrinolysis are in progress, platelet counts and fibrinogen levels may be normal or only marpinally reduced although levels of FIDP are elevated[10],[11],[12],[13],[28]. These patients rarely bleed spontaneously or from minor trauma, but have severe haemorrhage if subjected to surgery[30].

Decompensated DIC: Haemorrhage from multiple sites is the dominant manifestation. It commonly starts as bleeding from puncture sites after intravenous or intramuscular injections, and from the postpartum uterus or surgical wounds. Bleeding from mucosal sites follows, with gastric haemorrhage being the commonest [Table - 2]. Haematuria is also common, particularly in obstetric patients and following snake bite (unpublished observations). In severe DIC large ecchymoses and intracranial bleeding may occur[11],[12].

In severe cases, DIC is invariably accompanied by shock, either due to the underlying disorder or due to massive blood loss[9],[26]. Hypotension if prolonged can result in organ ischemia and dysfunction and acute tubular necrosis is common in this setting. The thrombotic manifestations of DIC may worsen organ hypoperfusion and severe renal insufficiency with acute cortical necrosis may result[11],[12]. Other manifestations of microvascular thrombosis are worsening of consciousness in the absence of focal neurological signs, cutaneous infarcts, acrocyanosis and gangrene

'Purpura fulminans' is the term used to describe a variant of DIC where the thrombotic manifestations predominate and is commonly seen in severe meningococcal infections[16],[17],[31]. Thrombocytopenia and coagulopathy are detectable on laboratory tests.

Chronic DIC: This refers to conditions where mild bleeding and abnormal coagulation tests suggestive of low grade DIC persist for many weeks[9],[32]. Malignancy is the major cause of this syndrome classically associated with acute promyelocytic leukemia, prostatic carcinoma and mucinous adenocarcinoma[32],[26].

  ::   Laboratory investigations Top

The laboratory diagnosis is based on demonstration of the 3 hallmarks of DIC - depletion of clotting factors, thrombocytopenia and increased FDP in circulation[10],[13]. The prothrombin time tests the extrinsic pathway and is abnormal in over 90% of patients with decompensated DIC[7],[26]. It is also prolonged in liver disease but may be normal in mild or compensated DIC[13]. The partial thromboplastin time, like the whole blood clotting time, tests the integrity of the intrinsic pathway. It is particularly sensitive to deficiencies of factors IX and VIII[13]. Being more sensitive than whole blood clotting time, it is prolonged in a majority of cases of decompensated DIC[33]. Thrombin time measures the time taken for a standard thrombin solution to convert fibrinogen to fibrin[13]. It depends on fibrinogen levels and on presence of inhibitors of this reaction like FDP Serum fibrinogen level also indicates the extent of depletion of clotting factors, and is of prognostic significance[11],[12]. It also guides therapy. Levels of less than 150 mg/dl occur in about 70% of patients with DIC[9].

Thrombocytopenia may be evident on peripheral smear -each platelet seen in an oil immersion field (1000x) corresponds to a count of 10,000 platelets per emm. Schistocytes or fragmented red blood cells may be seen in 50% of cases and indicates microcirculatory thrombosis[21],[22],[33]. Platelet count more accurately reflects the extent of platelet depletion. Counts of less than 1,00,000 per cmm are found in about 90% of cases[9],[26].

Tests for fibrinolysis include the euglobin lysis time, which is the time taken to lyse a clot artificially prepared from the euglobin proteins in plasma, which precipitate when plasma is diluted and slightly acidified. Normally, this is in excess of 1 hours, but in DIC lysis occurs faster and values less than 30 minutes are significant[13]. Soluble fibrin monomers in circulation may be demonstrated by the plasma paracoagulation or ethanol gelation tests in 50% of cases[33]. Tests for FDP in serum include the Thrombo-Wellcotest which estimates fragment D and E levels and the staphylococcal clumping test which estimates fragment X and Y levels[13]. Levels greater than 5 ug/ml are seen in 95% of patients and values above 40 ug/ml are confirmatory[9],[12].

Prothrombin time, serum fibrinogen levels and a platelet count have been recommended as screening tests. Abnormality in all three in the absence of liver disease or dilution due to severe blood loss, indicate definite DIC[7]. If only two of these tests are abnormal, further confirmatory tests are required. These include tests for FDP levels, thrombin time or euglobin lysis time[9]. Estimation of individual clotting factor or antithrombin III levels are rarely required in clinical practice.

  ::   Diagnosis Top

Mucosal bleeding along with renal and cerebral dysfunction can also occur in thrombotic thrombocytopenic purpura[34]. This is a thrombotic disorder that complicates a number of collagen diseases and viral or bacterial infections[15],[16] and an abnormality in the vessel wall or platelets is thought to be responsible for platelet aggregation. As in DIC, the peripheral smear shows thrombocytopenia and schistocytes. Unlike in DIC, prothrombin and partial thromboplastin time are normal in over 90% of cases and fibrinogen levels are low in less than 5%[35].

Coagulopathy in liver disease is usually due to inadequate hepatic synthesis of clotting factors[36]. However, DIC may occur in some patients because of inadequate synthesis of antithrombin III and decreased clearance of activated clotting factors and plasminogen activators[12],[36]. Thrombocytopenia and FDP levels may help in differentiating between these conditions[11], but splenic sequestration of platelets may make this distinction blurred. Estimation of factor VIII levels is useful - it is low in DIC[34],[37] but normal in liver disease due to its synthesis at non- hepatic sites[38].

Primary fibrinogenolysis may occur in many conditions which also cause DIC like snake bite, prostatic carcinoma or prostatic surgery, mucinous adenocarcinomas and large haemangiomas[12],[39]. Fibrinogen is lysed without accompanying microcirculatory thrombosis. Antifibrinolytic agents which are contraindicated in DIC are extremely useful in this condition[12]. As in DIC, these patients too have prolonged prothrombin and partial thromboplastin times, low serum firbrinogen levels and elevated serum FDP levels. However, the platelet count in primary fibrinogenolysis is near normal[39].

  ::   Treatment Top

The wide range of manifestations ranging from thrombosis to haemorrhage, difficulty in quantifying response to therapy, presence of coexisting multiple organ failure and varying prognosis of the underlying disease have made systematic evaluation of any therapeutic modality difficult. Very few controlled trials exist and most recommendations are empiric, thus remaining controversial.

General measures: If there is any unanimity among authors, it is regarding vigorous treatment of the underlying disease that initiated the DIC[7],[8],[9],[10],[12],[25]. This is particularly evident in patients with abruptio placentae or retained dead foetus where bleeding ceases promptly after delivery[33]. On the other hand, control of septicemia may not be that easy to achieve. Coexisting conditions that worsen DIC like hypovolaemia h potension, hypoxia and acidosis should be corrected[12]. Infusions of dextran 75 and gelatin should be avoided as they may worsen bleeding[40].

Blood component therapy: Replacement of depleted blood components seems to help control blood loss. This may be maximally evident only after the consumptive process has been interrupted[11],[12]. However, the suggestion that component therapy in patients with continuing consumption may 'add fuel to the fire' by increasing microcirculation thrombosis and FDP production is poorly supported by published data. Bick[37] reported worsening of the coagulopathy after transfusion of prothrombin complex concentrates in a patient with cirrhosis and DIC.

However, this may reflect the presence of thromboplastic material in prothrombin concentrate [42] which can cause thrombosis even when used in haemophilia[43]. Fresh frozen plasma and cryoprecipitate are the preferred blood components[5],[6],[7],[8],[9],[10],[11],[12]. Fresh plasma provides all clotting factors and antithrombotic proteins. However, fibrinogen may not increase with replacement of plasma alone, because unlike other factors it is consumed by both activation and fibrinogenolysis by plasmin. Cryoprecipitate provides greater quantities of fibrinogen than plasma on a volume for volume basis; it is often required when serum fibrinogen level is very low to start with[8],[44].

A general recommendation is to start with 4 to 6 units of fresh frozen plasma and 2 to 3 units of cryoprecipitate and reassess the clotting profile[8],[9],[10]. The aim of therapy is to maintain fibrinogen levels above 100 mg/dl and a platelet count greater than 50,000 per ?l. A platelet count less than 50,000 per ?l, or persistent bleeding in spite of adequate firinogen levels indicate need for platelet transfusions[8],[9],[10]. One unit of fresh frozen plasma or cryoprecipitate raises fibrinogen levels by 15 mg/dl; one unit of platelets raises the count by 5000 to 10,000 per ?l[11],[12]. Any increase in fibrinogen levels after adequate replacement indicates that the consumption process has ceased and more transfusions may be useful[12]. On the other hand, if platelet count and fibrinogen level are unchanged, further transfusions may enhance thrombotic complications[8],[26]. Use of heparin should be considered at this stage[8]. Administration of fibrinogen alone does not help in DIC as other clotting factors too need to be replaced.

Heparin: Although consumption of coagulation factors may be interrupted with heparin therapy, the bleeding complications may increase, negating any benefit from the increase in clotting factor levels in blood[26]. Thus, the role of heparin in DIC has been the centre of controversy for over two decades[29],[45],[46]. No large controlled trials have been conducted. Small controlled trials by Gazzard et al [47] (22 patients) in DIC following liver failure due to paracetamol overdosage and by Warrell et al[48] in viper envenomation (14 patients) have shown that heparin has no beneficial effect on the clinical profile or coagulation tests. Retrospective analyses (some involving over 200 patients) have shown that heparin does not affect mortality[29],[49]. On the other hand, other authors mention that heparin may increase bleeding[25],[29]. This was also the conclusion of a controlled trial by Straub[50].

The only definite indication for use of heparin is DIC due to acute promyelocytic leukernia[51]. However, recently, this too, has been challenged[52]. It may also be useful in patients with predominant thrombotic features like purpura fulminans, worsening renal function or consciousness, presence of acrocyanosis or gangrene of extremeties and in patients with chronic DIC[8],[8],[10]. A less certain indication is when platelet count and fibrinogen level do not increase despite adequate blood component therapy [8],[11],[12], Results for this indication have been the poorest in DIC complicating systemic sepsis[6], A more controversial indication is for prophylaxis (5000 units subcutaneously 8 to 12 hourly) in patients with a definite predisposing condition, but in whom DIC is mild and bleeding is absent as in mismatched blood transfusion, heat stroke and amniotic fluid embolism[10],[33]. Surgery in the immediate past and head injury are relative contraindications for heparin use[53].

Cash[8] recommends an initial dose of 500 units per hour for 3 hours. If bleeding does not worsen and the fibrinogen level does not increase, it may be increased to 1000 units per hour provided aggressive replacement of blood components is possible. A few authors suggest that smaller doses of heparin (5 units/kg/hour) may decrease haemorrhagic complications[34],[54]. Heparin acts by enhancing the effect of antithrombin III[55]. Antithrombin III is depleted in DIC[18]. Therefore, a majority of authors believe that DIC is a heparin-resistant state and doses as high as 3000 units per hour have been used[11],[12],[56]. Recent strategies to correct this resistance include infusion of antithrombin III after which, doses as low as 100 units of heparin per hour have proved effective[57],[58].

Coagulation tests like whole blood clotting time and partial thromboplastin time may be further prolonged with heparin[59]. Rising fibrinogen levels may therefore be the only reliable parameter to monitor efficacy of heparin therapy. Reptilase time (time taken for blood to coagulate after addition of the venom of the snake Bothrops atrox which directly converts fibringogen to fibrin) is another useful test to monitor coagulation because unlike thrombin time, it is not affected by heparin[59].

Antithrombin III: About 90% of patients with DIC have very low serum antithrombin III levels[18],[57],[58]. This may be an important factor, which sustains the coagulopathy. Over half a dozen studies in obstetric and non-obstetric DIC have shown that simultaneous infusion of antithrombin III and heparin produce clinical improvement and correction of coagulation defects within 2 hours[33],[57],[58]. The initial dose of 2500 units of antithrombin III (40 mg/kg) is followed by a continuous infusion of 50 units/hour.

Antifibrinolytic agents: Epsilon aminocaproic acid (C ACA) and tranexamic acid compete with fibrin for the lysine binding sites on plasminogen[12]. They also prevent plasmin from acting on fibrin and fibrinogen. Initial studies using EACA in DIC showed that it produced fatal widespread thrombosis as a result of inhibition of thrombolysis while the excessive coagulation persisted unchecked[60],[61],[62]. Thus, antithrombolytic drugs are contraindicated in DIC, although they remain drugs of choice in primary fibrinolysis where fibrinogen is lysed in the absence of thrombosis[12],[39],[51]. The dose is 4-6 g of EACA initially followed by 1 g every 1 to 2 hours for 48 hours. No studies have tried antithromblytic drugs after initial anticoaguiation[12].

Aprotinin: In addition to being a potent antiplasmin agent, this drug also has anticoagulant properties[63] and is therefore thought to help re-establish homeostatic equilibrium between coagulation and fibrinolysis[64]. Thus, it seems to be the ideal drug for treatment of DIC. Sher and Statland[64] strongly recommend the use of aprotinin in DIC due to abruptio placentae, especially in the 20% of women with abruptio placentae who develop uterine hypotonicity which aggravetes blood loss. This is resistant to usual oxytocics, and is generally associated with FDP levels in excess of 320 ug/ml Aprotinin (Trasylol) in a dose of 1 million units promotes haemostasis as well as enhances uterine contraction[64]. It has however not found widespread usage.

Other measures: Corticosteroids have been tried and may worsen DIC[65]. Exchange transfusion has been used successfully in neonates with DIC, especially in presence of renal failure when blood component therapy may worsen hypervolemia[53]. Antiplatelet drugs have no role in M although they may be of some benefit in thrombotic thrombocytopenic purpura[51]. Synthetic serine protease inhibitors - gabexate mesilate and nafamostat mesilate are being tried and may prove useful in the future[32]. Low molecular weight heparins, which produce less haemorrhagic complications than native heparin, may also prove useful in the future[66].

Surgery: Operative surgery in a patient with established DIC could be dangerous. However, active intervention may be helpful in obstetric DIC; in patients with a retained dead foetus surgical delivery usually terminates the DIC. In non-obstetric cases, the experience of Stone et al[67] of 31 patients with abdominal trauma or bacterial peritonitis who developed DIC and haemorrhage during laparotomy, is significant. In their first 14 patients, they continued to operate while blood and components were being transfused. Thirteen of these patients died. In the next 17 patients, they immediately terminated the operation - vital vessels were repaired, other vessels were ligated, open bowel ends were closed with purse-string sutures as in appendicectomy and no drains were placed. I nstead, 4 to 17 laparotomy pads were packed into the abdomen and the abdomen was closed under tension, in 3 layers. Patients were re-explored after they stabilized (mean 27 hours, range 15-69 hours). Wound infection developed in 12, intra-abdominal abscesses in 9 and empyema in 1. Many needed mechanical ventilation because abdominal tension interfered with breathing. However, 13 of the 17 survived. The need for whole blood was 25% of that in the other group, plasma 50% and packed red cells 60%[67], Thus, it seems prudent to defer surgery till the patient stabilizes. In abdominal infection with septicemia and DIC, limited drainage may be all that is needed.

In our own experience, curettage may be safe in obstetric cases. However, 7 of 10 (70%) patients who underwent Caesarean section died, as did all 3 patients who underwent hysterectomy, one who had suturing of a perforated duodenal ulcer and one with suturing of uterine tears.

  ::   Prognosis Top

The prognosis depends mainly on the underlying condition. Nevertheless, very low fibrinogen levels, post-operative DIC, coexisting hypotension, multiple organ failure, and systemic sepsis carry a poor prognosis. The overall mortality varies from 50 to 80 percent[5],[26],[44]. In our experience, the mortality in nonobstertric cases is 45.2% and in obstetric cases is 54.2%.

In conclusion, DIC is one of the many facets of multiple system organ failure, which occurs in critically ill patients. As facilities for intensive care expand, we, in India, are likely to encounter more cases of DIC, On the other hand, obstetric diseases and snake bite are common, and since these occur in previously healthy persons, vigorous therapy may produce excellent results. Easy availability of blood products including platelets after the establishment of the National Plasma Fractionation Centre in Bombay have helped reduce overall mortality in our series from 70% in 1985-86 to 40% in 1990-91. The possibility that measures to control DIC may worsen function of other organs should always be kept in mind. With a clearer understanding of the underlying abnormalities than we have today, newer, more effective drugs are likely to emerge in the near future. Till then, therapy will be restricted largely to blood components and heparin.

  ::   Acknowledgment Top

We thank the Dean, King Edward Memorial Hospital for permitting us to publish data from hospital records.

 :: References Top

1. McKay DG. Disseminated intravascular coagulation. New York: Harper and Row; 1965; 472-480.  Back to cited text no. 1    
2.Sirridge MS, Shannon RG. Laboratory evaluation of haemostasis and thrombosis, 3rd edition. Philadelphia: Lea and Febiger; 1983, pp 1-16.  Back to cited text no. 2    
3.Colman RW, Marder VJ, Salzman EW, Hirsh J. Overview of hemostasis. In: Colman RK Hirsh J, Marder VJ, Saizman EW, editors. Hemostasis and Thrombosis - Basic Principles and Clinical Practice, 2nd ed. Philadelphia: JB Lippincott; 1987, pp 3-17.  Back to cited text no. 3    
4.Deykin D. The clinical challenge of DIC. N Engl J Med 1970; 282:636-644.  Back to cited text no. 4    
5.Ulrich A. Antithrombin and related inhibitors of coagulation. In: Poller L, editor. Recent advances in Blood Coagulation. 2, Edinburgh: Churchill Livingstone; 1981; 151-173.  Back to cited text no. 5    
6.Greengard JS, Griffin H. Protein C pathways. In: Hoffibrand AV, editor. Recent Advances in Haematology, 5, Edinburgh: Churchill Livingstone; 1988, pp 275-289.  Back to cited text no. 6    
7.Lazarchuk J, Kizer J. Interaction of fibrinolytic, coagulation and kinin systems and related pathology. In: Pittiglio DH, Sacher RA Eds. Clinical Hematology and Fundamentals of Hemostasis. Philadelphia: FA Davis; 1987, pp 381-391.  Back to cited text no. 7    
8.Cash JD. Disseminated intravascular coagulation. In: Poller L Ed. Recent Advances in Blood Coagulation, 2, Edingburgh: Churchill Livingstone; 1977, pp 293-312.  Back to cited text no. 8    
9.Coliman RW, Robboy SJ, Minna JD. Disseminated Intravascular Coagulation - a reappraisal. Ann Rev Med 1979; 30:359-374.  Back to cited text no. 9    
10.Sharp AA. Diagnosis and management of disseminated intravascular coagulation. Br Med Bull 1977; 33:265-272.  Back to cited text no. 10    
11.Marder VJ. Consumptive thrombohemorrhagic disorders. In: Williams WJ, Beutier E, Ersler AJ, Lichtman MA, editors. Hematology, 4th ed. Philadelphia: JB Lippincott; 1989, pp 1522-1543.  Back to cited text no. 11    
12.Marder VJ, Martin S, Francis CW, Colman RW. Consumptive thrombohemorrhagic disorders. In: colman RK Hirsh J, Marder VJ, Saizman EW, editors. Hemostasis and Thrombosis - Basic Principles and Clinical Practice, 2nd ed. Philadelphia: JB Lippincott; 1987, pp 975-1015.  Back to cited text no. 12    
13.Sirridge MS, Shannon RG. Laboratory evaluation of Hemostasis and Thrombosis, 3rd ed. Philadelphia: Lea and Febiger; 1983, pp 17-57.  Back to cited text no. 13    
14.Mann KG, Lundblad RL. Biochemistry of thrombin. In: Colman RW, Hirsh J, Marder VJ, Saizman EW, editors. Hemostasis and Thrombosis - Basic Principles and Clinical Practice, 2nd ed. Philadelphia: JB Lippincott; 1987, pp 148-161.  Back to cited text no. 14    
15.Beller FK. Sepsis and coagulation. Clin Obstet Gynecol 1985; 26:46-52.  Back to cited text no. 15    
16.Beck EA, Dejana E. Thrombohemorrhagic phenomena associated with infectious diseases. Semin Hematol 1988; 25:91-100.  Back to cited text no. 16    
17.Pareti FI, Capitanio A, Mannucci PM. Acquired storage pool diseases in platelets during disseminated intravascular coagulation. Blood 1976; 48:511-515.  Back to cited text no. 17    
18.Bick RL, Bick MD, Fekete LF. Antithrombin III patterns in disseminated intravascular coagulation, Am J Clin Pathol 1980; 73:577-583.  Back to cited text no. 18    
19.Marlar RA, Endres-Brooks J, Miller C. Serial studies of protein C and its plasma inhibtor in patients with disseminated intravascular coagulation. Blood 1985; 66:59-63.  Back to cited text no. 19    
20.Rudenberg ML, Regoeczi E, Bull BS, Dacie JV, Brain MC. Micriangiopathic haemolytic anaemia: the experimental production of haemolysis and red cell fragmentation by defibrination in vivo. Br J Haematol 1968; 14:627-642.  Back to cited text no. 20    
21.Rabiner SF, Friedman LH. The role of intravascular hemolysis and the reticuloendothelial system in the production of a hypercoagulable state. Br J Haematol 1968; 14:105-118.  Back to cited text no. 21    
22.Gane H, Lowman JT. The uptake of fibrin and fibrin degradation by the isolated perfused rat liver. Blood 1967; 26:526-539.  Back to cited text no. 22    
23.Sherman LA, Lee J. Fibronectin: blood turnover in normal animals during intravascular coagulation. Blood 1982; 60:558-563.  Back to cited text no. 23    
24.Mosher DF, Williams EM. Fibronectin concentration is decreased in plasma of severely ill patients with disseminated intravascular coagulation. J Lab Clin Med 1978; 91:729-735.  Back to cited text no. 24    
25.Mant MJ, King EG. Severe acute disseminated intravascular coagulation. Am J Med 1979; 67:557-563.  Back to cited text no. 25    
26.Coliman Rw, Robboy SJ, Minna JD. Disseminated intravascular coagulation: an approach. Am J Med 1972; 52: 679-689.  Back to cited text no. 26    
27.Kulkarni SD, Mahaian TA, Karnad DR, Tilve GH. Multiple organ system failure following obstetric diseases: experience of an urban referral center (Abstract). In: Abstracts of the first national conference on Integrated Care of the Critically III, Mumbai, 1989.  Back to cited text no. 27    
28.Cooper HA, Bowie EJ, Owen CA. Evaluation of patients with increased fibrinolytic products in their serum. Mayo Clin Proc 1974; 49:654-657.  Back to cited text no. 28    
29.Bang NU. Diagnosis and management of thrombosis. In: Shoemaker WC, Ayers S, Grenvik A, Holbrook PR, Thompson WI, editors. Textbook of Critical Care, 2nd ed. Philadelphia: WB Saunders; 1989, pp 886-895.   Back to cited text no. 29    
30.Fisher DF, Yawn DH, Crawford S. Preoperative disseminated intravascular coagulation associated with aortic aneurysms. Arch Surg 1983; 118:1252-1255.   Back to cited text no. 30    
31.Parikh DA, Fernandez RJ, Bhata SJ, Karnad DR, Dastur FD. Purpura fulminans. Indian J Dermatol Venerol and Leprol 1988; 54:30-32.  Back to cited text no. 31    
32.Sack GH, Levin J, Bell WR. Trousseau's syndrome and other manifestations of chronic disseminated coagulation in patients with neoplasms. Medicine 1977; 56:1-37.  Back to cited text no. 32    
33.Finley BE. Acute coagulopathy in pregnancy. Med Clin North Am 1989; 73:723-743.  Back to cited text no. 33    
34.Bick RL. Disseminated intravascular coagulation and related syndromes. Am J Hematol 1978; 51:265-282.  Back to cited text no. 34    
35.Eisenstadt RJ, Coiman RW, Marder VJ. Thrombotic thrombocytopenic purpura. In: Colman RW, Hirsh J, Marder VJ, Saizman EW, editors. Hemostasis and Thrombosis - Basic Principles and Clinical Practice, 2nd ed. Philadelphia: JB Lippincott; 1987, pp 1016-1025.  Back to cited text no. 35    
36.Veratraete M, Vermyien J, Collen D. Intravascular coagulation in liver disease. Ann Rev Med 1974; 25:447-455.  Back to cited text no. 36    
37.Hamilton PJ. Disseminated intravascular coagulation: a review. J Clin Pathol 1978; 31:609-619.  Back to cited text no. 37    
38.Maisonneuve P, Sultan Y. Modification of factor VIII complex properties in patients with liver disease. J Clin Pathol 1977; 30:221-227.  Back to cited text no. 38    
39.Kernoff PBA, MeNicol GP. Normal and abnormal firbinolysis. Br Med Bull 1977; 33:239-244.  Back to cited text no. 39    
40.Moriau M, Rodhian J, Neol H, Masure R. comparative effects of dextrans, gelatin and stable plasma protein solutions (SPSS) in experimental disseminated intravascular coagulation (DIC). Vox Sanguinis 1974; 27:411-428.  Back to cited text no. 40    
41.Bick RL, Schmalhorst WR, Fekete LF. Disseminated intravascular coagulation and blood component therapy. Transfusion 1976; 16: 361-365.  Back to cited text no. 41    
42.Blatt PM, Lundblad RL, Kingdon HS, MeLean G, Roberts HR. Thrombogenic materials in prothrombin complex concentrates. Ann Intern Med 1974; 81:766-770.  Back to cited text no. 42    
43.Kasper CK. Postoperative thrombosis in hemophilia. BN Engl J Med 1973; 289:160.  Back to cited text no. 43    
44.Feinstein DI. Diagnosis and management of disseminated intravascular coagulation: role of heparin therapy. Blood 1982; 60:284-287.  Back to cited text no. 44    
45.Sherman LA, Wessler S, Avioli LV. Therapeutic problems in disseminated intravascular coagulation. Ann Intern Med 1973; 132:446-453.  Back to cited text no. 45    
46.Crawford GRM, Douglas AJ. Heparin and its current therapeutic role. In: Poiler L, editor. Recent Advances in Blood Coagulation, 2. Edinburgh: Chuchill Livingstone; 1977, pp 337-361.  Back to cited text no. 46    
47.Gazzard BG, Clark R, Borirakchanyavat V, Williams RA. Controlled trial of heparin therapy in the coagulation defect of paracetomal-induced hepatic necrosis. Gut 1974; 15:89-93.  Back to cited text no. 47    
48.Warrel DA, Pope HM, Prentice CRM. Disseminated intravascular coagulation caused by the carpet viper (Echis carinatus): trial of heparin. Br J Haematol 1976; 33: 335-342.  Back to cited text no. 48    
49.Corrigan JJ. Heparin therapy in bacterial septicemia. J Pediatr 1977; 91:695-700.  Back to cited text no. 49    
50.Straub RW. A case against heparin therapy of intravascular coagulation. Thromb Diath Hemorrhage 1974; 33:107-112.  Back to cited text no. 50    
51.Kazmier FJ, Bowie EJMI, Hagedom AB, Owen CA. Treatment of intravascular coagulation and fibrinolytic syndromes. Mayo Clin Proc 1974; 81:766-770.  Back to cited text no. 51    
52.Tallman MS, Keaan HC. Reassessing the hemostatic disorder associated with acute promyelocytic leukemia. Blood 1992; 79:543-553.  Back to cited text no. 52    
53.Sarnaik AP, Stringer KD, Jewell PF, Sarnaik SA, Ravindranath Y. Disseminated intravascular coagulation with trauma: treatment with exchange transfusion. J Pediatr 1979; 63: 337-339.  Back to cited text no. 53    
54.Gurewich V, Lipinski B. Low-dose intravenous heparin in the treatment of disseminated intravascular coagulation.  Back to cited text no. 54    
55.Rosenberg RD. Actions and interaction of antithrombin and heparin. N Engl J Aled 1978; 31:609-619.  Back to cited text no. 55    
56.Klein HG, Bell WR. Disseminated intravascular coagulation during heparin therapy. Ann Intern Med 1974; 80:477-478.  Back to cited text no. 56    
57.Haak HL, Stolk JC, Gratama JW, van Hulsteyn H, Briet E. Use of antithrombin III concentrates in stable diffuse intravascular coagulation. Acta Haematol 1982; 68:28-33.  Back to cited text no. 57    
58.Schipper HG, Jenkins CSP, Kehie LM, Cate JWT. Antithrombin III transfusion in Disseminated intravascular coagulation. Lancet 1978; 1:854-856.  Back to cited text no. 58    
59.Grainick HR. Intravascular coagulation. Postgrad Med 1977; 62:68-87.  Back to cited text no. 59    
60.Grainick HR, Greipp P. Thrombosis with epsilon aminocaproic acid therapy. Am J Clin Pathol 1971; 56:151-154.  Back to cited text no. 60    
61.Charyton C, Purtilo D. Glomerular capillary thrombosis and acyte renal failure after epsilon aminocaproic acid therapy. N Engl J Med 1969; 280:1102-1104.  Back to cited text no. 61    
62.Naeye RL. Thrombotic state after haemorrhagic diathesis, possible complication of therapy with epsilon aminocaproic acid. Blood 1962; 19:694-701.  Back to cited text no. 62    
63.Dubber AHG, McNicol GP, Uttley D, Douglas AS. In vitro and in vitro studies with trasylol, an anticoagulant and a fibrinolytic inhibitor. Dr J Haemaol 1968; 14:31-49.  Back to cited text no. 63    
64.Sher G, Statiand BE. Abruptio placentae with coagulapathy: a rational basis for management. Clin Obstet Gynecol 1985; 28:15-23.  Back to cited text no. 64    
65.Blix S, Jacobsen Cd. intravascular coagulation, a possible accelerating effect of prednisone. Acta Med Scand 1966; 180:723-728.  Back to cited text no. 65    
66.Nieuwenhuis HK, Sixma JJ. Treatment of disseminated intravascular coagulation in acute promyelocytic leukemia with low molecular weight heparinoid ORG 10172. Cancer 1986; 58:761-764.  Back to cited text no. 66    
67.Stone HH, Strom PR, Mullins RJ. Management of the major coagulopathy with onset during laparotomy. Ann Surg 1983; 197:532-535.   Back to cited text no. 67    


[Figure - 1]


[Table - 1], [Table - 2]


Print this article  Email this article
Previous article Next article
Online since 12th February '04
2004 - Journal of Postgraduate Medicine
Official Publication of the Staff Society of the Seth GS Medical College and KEM Hospital, Mumbai, India
Published by Wolters Kluwer - Medknow