Abstract
Blood coagulation studies were undertaken in patients of highaltitude pulmonary oedema at 3, 700 m, comparable controls, and sea level subjects to determine the possible causal connection between changes in fibrinolytic activity, blood coagulation factors, and formation of thrombi within the alveolar capillaries, venules and some branches of pulmonary arteries. The following changes have been observed: Fibrinolytic acitivty was reduced. Plasma fibrinogen and factor VIII were increased. Factor XII was decreased. Platelet adhesiveness and platelet factor 3 were increased and electrophoretic mobility of platelets reduced. The integrity of platelet plasma membrane and release reaction remained intact. Both arterial and venous ADP levels were low and there was evidence of excessive utilisation of ADP in the pulmonary bed. The findings suggest that sludging of RBCs and formation of thrombi possibly result from these changes, impede the pulmonary blood flow, and aggravate the disease.
Zusammenfassung
An Patienten mit Lungenödem und vergleichbaren Kontrollen in 3700 m Höhe und Personen in Meereshöhe wurden Blutgerinnungsstudien vorgenommen, um die möglichen kausalen Beziehungen zu bestimmen zwischen den Veränderungen der fibrinolytischen Aktivität, den Gerinnungsfaktoren und der Bildung von Thromben im arteriellen und venösen Teil der Alveolarkapillaren und einiger Äste der Pulmonalarterien. Folgende Änderungen wurden gefunden: die fibrinolytische Aktivität war vermindert; Plasmafibrinogen und Faktor VIII waren erhöht; Faktor XII war vermindert; Plättchenklebrigkeit und Plättchenfaktor 3 waren erhöht und die elektrische Beweglichkeit der Plättchen herabgesetzt. Die Plasmamembran der Plättchen und die Release-Reaktion bleiben unbeschädigt. Der arterielle und venöse ATP-Spiegel waren niedrig und es zeigten sich Hinweise auf vermehrte ATP-Utilisation in den Pulmonargefässen. Die Ergebnisse deuten darauf hin, dass als Folge der Veränderungen die Erythrozyten träge werden und sich Thromben bilden. Dies hemmt den pulmonalen Blutstrom und verstärkt die Krankheit.
Resume
On a mesuré les différentes propriétés de coagulation du sang de patients atteints d'oedème pulmonaire et de gens en santé (contrôle) et cela aussi bien à 3700 m d'altitude qu'au bord de la mer. Ces essais ont été effectués pour déterminer les relations de cause à effet possibles entre les changements de l'activité fibrinolytique et des facteurs de coagulation du sang d'une part, la formation de thromboses dans les capillaires alvéolaires, les veinules et diverses branches des artères pulmonaires d'autre part. On a alors pu observer les modifications suivantes chez les personnes du premier groupe (malades) : l'activité fibrinolytique est réduite, la fibrinogène du plasma et le facteur VIII sont augmentés, le facteurs XII est diminué, l'adhésivité des plaquettes et le facteur 3 des plaquettes sont augmentés et la mobilité électrophorétique des plaquettes est réduite. L'intégrité des membranes plasmatiques des plaquettes et la réaction de décontraction sont restées inchangées. Le niveau de l'ADP aussi bien artériel que veineux a été très bas ce qui démontre une surconsommation au niveau des poumons. Les résultats obtenus laissent à penser que, par suite des modifications mentionnées, les érythrocytes perdent de leur vitalité et que des thromboses se forment. Ceci a pour conséquence de ralentir le flot sanguin pulmonaire et d'aggraver la maladie.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
BORN, G.V.R. (1968): Platelet membrane and its functions. In: Plenary Sessions Papers. E.R.Jaffe (ed.), XII Congress International Society of Hematology, New York, 95–110.
CUNNINGHAM, W.L., BECKER, E.J. and KREUZER, F. (1965): Catecholamines in plasma and urine at high altitude. J.appl. Physiol., 20: 607–610.
De GAETANO, G., VERMYLEN, J. and VERSTRAETE, M. (1970a): Inhibition of platelet aggregation - its potential clinical usefulness: a review. Hematologic reviews. Marcel Dekker, New York, 205–232.
De GAETANO, G., VERMYLEN, J. and VERSTRAETE, M. (1970b): Platelet aggregation by a specific human immunoglobulin preparation. Thromb. Diath. Haemorrh., 24: 419–431.
GARVEY, M.B., DENNIS, L.H. and CONRAD, M.E. (1958): The coagulopathy of hypobaric induced polycythemia and its reversal with heparin. Clin. Res., 16: 370.
GENTON, E., ROSS, A.M., TAKEDA, Y.A. and VOGEL, J.H.K. (1970): Alterations in blood coagulation at high altitude. In: Advances in Cardiology. Hypoxia, High Altitude and the Heart. J.H.K. Vogel and S. Barbara (ed.), Karger, Basel, pp.32–40.
GROVER, R.F. and ALEXANDER, J.A. (1970): Quoted by Genton et al. (ibid).
HARDISTY, R.M. (1968): Platelet aggregation and platelet factor 3 availability in bleeding disorders. Exp.Biol. Med., Vol.3, Karger, New York, 3: 189–192.
HARDISTY, R.M. and HUTTON, R.A. (1966): Platelet aggregation and the availability of platelet factor 3. Brit.J.Haemat., 12: 764–776.
HASLAM, R.J. (1964): Role of adenosine-diphosphate in the aggregation of human blood-platelets by thrombin and by fatty acids. Nature (Lond.), 202: 765–768.
HOAK, J.C., WARNER, E.D. and CONNOR, W.E. (1967): Platelets, fatty acids, and thrombosis. Circulation Res., 20: 11–17.
HOROWITZ, H.I. and PAPAYOANOU, M.F. (1968): Activation of platelet factor 3 by adenosine 5′ diphosphate. Thromb. Diath. Haemorrh., 19: 18–28.
HURTADO, A. (1932): Studies at high altitude. Blood observations on Indian natives of Peruvian Andes. Amer.J.Physiol., 100: 487–505.
IATRIDIS, P.G. and FERGUSON, J.H. (1965): The plasmatic atmosphere of blood platelets. Evidence that only fibrinogen, AcG and activated Hageman factor are present on the surface of platelets. Thromb. Diath. Haemorrh., 13: 114–125.
KEMP, G.T. (1902): Relation of blood platelets to the increase in the number of red corpuscles at high altitudes. Proc. Amer.Physiol.Soc. 14th Ann.Meeting, Univ.of Chicago, Dec.1901. Amer.J.Physiol., 6: 11–12.
KINGMA, H. and DE LANGEN, C.D. (1955): Hypoxia and bloodcoagulation. Aeromed. Acta., 4: 98–104.
MARCUS, A.J., ZUCKER-FRANKLIN, D., SAFIER, L.B. and ULLMAN, H.L. (1966): Studies on human platelet granules and membrane. J.clin.Invest., 45: 14–28.
MITCHELL, J.R.A. and SHARP, A.A. (1964): Platelet clumping in vitro. Brit. J.Haemat., 10: 78–93.
MUSTARD, J.F. and PACKHAM, M.A. (1968): Biochemistry of primary hemostasis. Plenary Sessions Papers. XII Congress International Society of Hematology, New York, pp.306–314.
NAYAK, N.C., ROY, S. and NARAYANAN, T.K. (1964): Pathologic features of altitude sickness. Amer.J.Path., 45: 381–391.
O'BRIEN, J.R. (1963): Some effects of adrenaline and antiadrenaline compounds on platelets in vitro and in vivo. Nature (Lond.), 200: 763–764.
PACE, N., GRISWOLD, R.L. and GRUNBAUM (1964): Increase in urinary norepinephrine excretion during 14 days sojourn at 3, 800 metres elevation. Fed.Proc., 23: 521 (no 2516).
POPLAWSKI, A., SKORULSKA, M. and NIEWIAROWSKI, S. (1968): Increased platelet adhesiveness in hypertensive cardiovascular disease. J.Atheroscler.Res., 8: 721–723.
PROKOPOWICZ, J., WOROWSKI, K., POPLAWSKI, A., GABRYELEWICZ, A. and NIEWIAROWSKI, S. (1967): Fibrinolytic system in patients with hypertensive cardiovascular disease. Thromb.Diath.Haemorrh., 17: 1–7.
SALZMAN, E.W. and LEVINE, L. (1971): Cyclic 3′–5′-adenosine monophosphate in human blood platelets. II. Effect of N6-2′-0-dibutyryl cyclic 3′–5′-adenosine monophosphate on platelet function. J.clin.Invest., 50: 131–141.
SALZMAN, E.W. and NERI, L.L. (1969): Cyclic 3′–5′-adenosine monophosphate in human blood platelets. Nature (Lond.), 224: 609–610.
SCHOENMAKERS, J.G.G., MATZE, R., HAANEN, C. and ZILLIKEN, F. (1965): Hageman Factor, a novel sialoglycoprotein with esterase activity. Biochim. biophys.Acta (Amst.), 101: 166–176.
SHORE, P.A. and ALPERS, H.S. (1963): Platelet damage and release of amines by mocrogram quantities of certain fatty acids. Fed. Proc., 22: 504.
SINGH, I. (1967): High-altitude pulmonary oedema. Z.Kreisl.-Forsch., 56: 1234–1243.
SINGH, I. and CHOHAN, I.S. (1972a): Abnormalities of blood coagulation at high altitude. Int.J.Biometeor., 16: 283–297.
SINGH, I. and CHOHAN, I.S. (1972b): Blood coagulation changes at high altitude predisposing to pulmonary hypertension. Brit.Heart J., 34: 611–617.
SINGH, I., KAPILA, C.C., KHANNA, P.K., NANDA, R.B. and RAO, B.D.P. (1965a): High-altitude pulmonary oedema. Lancet, 1: 229–234.
SINGH, I., KHANNA, P.K., MADAN LAL, HOON, R.S. and RAO, B.D.P. (1965b): High-altitude pulmonary hypertension. Lancet, 2: 146–150.
SINGH, I., KHANNA, P.K., SRIVASTAVA, M.C., MADAN LAL and ROY, S.B. (1969): Acute mountain sickness. New Engl.J.Med., 280: 175–184.
SURKS, M.I., BECKWITT, H.J. and CHIDSEY, C.A. (1967): Changes in plasma thyroxine concentration and metabolism, catecholamine excretion and basal oxygen consumption in man during acute exposure to high altitude. J.clin.Endocr., 27: 789–799.
SURTSHIN, A., RODBARD, S. and KATZ, L.N. (1948): Inhibition of epinephrine action in severe hypoxemia. Amer.J.Physiol., 152: 623–632.
SUTHERLAND, E.W. (1965): Adenyl cyclase and hormone action. In: Pharmacology of Cholinergic and Adrenergic Transmission. G.B.Koelle, W.W.Douglas and A.Carlsson (ed.), Macmillan (Pergamon), New York, p.317.
VAN LOO, A., SURTSHIN, A. and KATZ, L.N. (1948): Nature of the two pressor responses to acute hypoxemia with some observations on the role of the adrenals in hypoxia. Amer.J. Physiol., 154: 397–404.
WHITTEN, B.K. and JANOSKI, A.H. (1969): Effect of high altitude and diet on lipid components of human serum. Fed.Proc., 28: 983–986.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Singh, I., Chohan, I.S. Adverse changes in fibrinolysis, blood coagulation and platelet function in high altitude pulmonary oedema and their role in its pathogenesis. Int J Biometeorol 18, 33–45 (1974). https://doi.org/10.1007/BF01450663
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01450663