Activation of Coagulation and Fibrinolysis in Heatstroke

Abderrezak Bouchama; Françoise Bridey; Muhammad M Hammami; Catherine Lacombe; Essam Al-Shail; Yazid Al-Ohali; Frédéric Combe; Sultan Al-Sedairy; Dominique de Prost

doi:10.1055/s-0038-1650685

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1996; 76(06): 0909-0915
DOI: 10.1055/s-0038-1650685

Original Article

Schattauer GmbH Stuttgart

Activation of Coagulation and Fibrinolysis in Heatstroke

Abderrezak Bouchama

¹The Department of Medicine, Biomedical and Medical Research, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

,

Françoise Bridey

²Service d’Hematologie et d’lmmunologie Biologiques et INSERM U294, CHU Xavier Bichat, Paris, France

,

Muhammad M Hammami

¹The Department of Medicine, Biomedical and Medical Research, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

,

Catherine Lacombe

²Service d’Hematologie et d’lmmunologie Biologiques et INSERM U294, CHU Xavier Bichat, Paris, France

,

Essam Al-Shail

¹The Department of Medicine, Biomedical and Medical Research, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

,

Yazid Al-Ohali

¹The Department of Medicine, Biomedical and Medical Research, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

,

Frédéric Combe

²Service d’Hematologie et d’lmmunologie Biologiques et INSERM U294, CHU Xavier Bichat, Paris, France

,

Sultan Al-Sedairy

¹The Department of Medicine, Biomedical and Medical Research, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

,

Dominique de Prost

²Service d’Hematologie et d’lmmunologie Biologiques et INSERM U294, CHU Xavier Bichat, Paris, France

› Author Affiliations

Abstract

PDF Download

Summary

Hemorrhagic diathesis and widespread microthrombosis are common in heatstroke. To assess the early stages of coagulopathy in heatstroke, thrombin-antithrombin III (TAT), fibrin monomers, plasmin-a2-antiplasmin (PAP), plasminogen and D-Dimer were measured in 16 heatstroke patients (means ± SE rectal temperature 42.3 ± 0.2° C) pre- and postcooling and compared with 8 heatstressed and 23 normal controls.

Comparing heatstroke patients with normal controls, TAT, fibrin monomers, PAP and D-Dimer were elevated to (median (range)) 16.5 (4-1000) versus 3.5 (2-7.2) Μg/l p<0.001,16 (4-113) versus 2 (2-9) nM p<0.001; 3300 (1000-36500) versus 255 (136-462) Μg/l p<0.001 and 0.72 (0.22-64.8) versus 0.15 (0.05-0.25) Μg/ml p<0.01 respectively. Plasminogen decreased to 81% (34-106); PAP, TAT and D-Dimer correlated significantly with hyperthermia (r = 0.577, p = 0.02; r = 0.635, p = 0.01; r = 0.76, p = 0.003). Postcooling PAP decreased to 545 (260-850) Μg/1 p<0.005, TAT 10 (6-70) |ig/l, and fibrin monomers 22 (18-86) nM remained unchanged. Heatstressed controls showed mild but significant increase in all markers.

Activation of coagulation and fibrinolysis occurs early and is profound and sustained in heatstroke. Cooling seems to attenuate the activation of fibrinolysis only, however, this requires confirmation in a larger study population.

PDF (376 kb)

References

References
1 Knochel JP. Heatstroke and related heatstress disorders. Dis Mon 1989; 35: 301-378
2 Bouchama A, Cafege A, DeVol EB, Labdi O, El-Assil K, Seraj M. Ineffectiveness of dantrolene sodium in the treatment of heatstroke. Crit Care Med 1991; 19: 176-180
3 Heat-Related Mortality, Chicago, July 1995. MMWR Morb Mortal Wkly Rep 1995 44. 577-579
4 Jimenez-Mejias ME, Montano Diaz M, Villalonga J, Bollain Tienda E, Lopez Pardo F, Pineda JA, Gonzales de la Puenta MA. Classical heatstroke in Spain. Analysis of a series 78 cases. Medicina Clinica 1990; 94: 481-486
5 Shibolet S, Fisher S, Gilat T, Bank H, Heller H. Fibrinolysis and hemorrhages in fatal heatstroke. N Engl J Med 1962; 266: 169-173
6 Meikle AW, Graybill JR. Fibrinolysis and hemorrhage in a fatal case of heat stroke. N Engl J Med 1967; 276: 911-913
7 Bachmann F. Evidence for hypercoagulability in heat stroke (Letter). J Clin Invest 1967; 46: 1033
8 Sohal RS, Chien Sun S, Colcolough HL, Burch GE. Heat Stroke: An electron microscopic study of endothelial cell damage and disseminated intra-vascular coagulation. Arch Intern Med 1968; 122: 43-47
9 Weber MB, Blakely JA. The haemorrhagic diathesis of heatstroke. A consumption coagulopathy successfully treated with heparin. Lancet 1969; 1: 1190-1192
10 Perchick JS, Winkelstein A, Shadduck RK. Disseminated intravascular coagulation in Heat stroke. Response to heparin therapy. JAMA 1975; 231: 480-483
11 Wright DO, Reppert LB, Cuttino JT. Purpuric manifestations of heatstroke. Studies of prothrombin and platelets in twelve cases. Arch Intern Med 1946; 77: 27-36
12 Beard MEJ, Hickton CM. Haemostasis in heatstroke. Br J Haematol 1982; 52: 269-274
13 Al-Mashhadani SA, Gader AGMA, Al-Harthi SS, Kangav D, Shaheen FA, Bogus P. The coagulopathy of heatstroke: alterations in coagulation and fibrinolysis in heat stroke patients during the pilgrimage (Haj) to Makkah. Blood Coag Fibrinol 1994; 5: 731-736
14 El-Kassimi FA, Al-Mashhadani S, Abdullah AK, Akhtar J. Adult respiratory distress syndrome and disseminated intravascular coagulation complicating heatstroke. Chest 1986; 90: 571-574
15 Chao TC, Sinniah R, Pakiam JE. Acute heatstroke deaths. Pathology 1981; 13: 145-156
16 Handin RI. Bleeding and Thrombosis. In: Harrison’s Principles of Internal Medicine, 12th Ed Wilson JD, Braunwald E, Isselbacher KJ, Petersdroff RG, Martin JB, Fauci AS, Root AK. eds. New York, NY: McGraw-Hill: 1990: 348-359
17 Takahashi H, Tatewaki W, Wada K, Hanamo M, Shibata A. Thrombin vs plasmin generation in disseminated intravascular coagulation associated with various underlying disorders. Am J Hematol 1990; 33: 90-95
18 Legall JR, Loirat P, Alperovitch A, Glaser P, Granthil C, Mathieu D, Mer-cier P, Thomas R, Villiers D. A simplified acute physiology score for ICU patients. Crit Care Med 1984; 12: 975-977
19 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol (Basel) 1957; 17: 237-246
20 Bouchama A, Cafege A, Robertson W, Al-Dossary S, El Yazigi A. Mechanisms of hypophosphatemia in humans with heatstroke. J Appl Physiol 1991; 71: 328-332
21 Weiner JS, Khogali M. A physiological body-cooling unit for treatment of heatstroke. Lancet 1980; 1: 507-509
22 Shifman MA, Pizzo SV. The in vivo metabolism of antithrombin III and antithrombin complexes. J Biol Chem 1982; 257: 3243-3247
23 Bedrak E, Beer G, Furman KI. Fibrinolytic activity and muscular exercise in heat. J Appl Physiol 1964; 19: 469-471
24 Bedrak E. Effect of muscular exercise in a hot environment on canine fibrinolytic activity. J Appl Physiol 1964; 20: 1307-1311
25 Strother SV, Bull JMC, Branham SA. Activation of coagulation during therapeutic whole body hyperthermia. Thromb Res 1986; 43: 353-360
26 van Deventer SJH, Buller HR, ten Cate JW, Aarden LA, Hack CE, Sturk A. Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic and complement pathways. Blood 1990; 76: 2520-2526
27 Bouchama A, Parhar RS, El-Yazigi A, Sheth K, Al-Sedairy S. Endotoxemia and release of tumor necrosis factor and interleukin-la in acute heatstroke. J Appl Physiol 1991; 70: 2640-2644
28 Bouchama A, Hammami M, Haq A, Jackson J, Al Sedairy S. Evidence for endothelial cell activation injury in heatstroke. Crit Care Med (in press)
29 Levi M, Cate HT, van der Poll T, van Deventer SJH. Pathogenesis of disseminated intravascular coagulation in sepsis. JAMA 1993; 270: 975-979
30 Levi M, ten Cate H, Bauer KA, Van Der Poll T, Edgington TS, Buller HR, van Deventer SJH, Hack CE, ten Cate JW, Rosenberg RD. Inhibition of endotoxin-induced activation of coagulation and fibrinolysis by pentoxifylline or by a monoclonal anti-tissue factor antibody in chimpanzees. J Clin Invest 1994; 93: 114-120
31 Ware JA, Heistad DD. Platelet-endothelium interactions. N Engl J Med 1993; 328: 628-635