Blood coagulation changes at high altitude predisposing to pulmonary hypertension.

Blood coagulation studies were carried out in 38 Indian soldiers who were resident at altitudes between I2,000 and i8,0oo feet for 2 years.Compared with I6 sea-level controls, 6 of these 38 subjects who had developed pulmonary hypertension during their stay at high altitude showed a significant increase ofplasmafibrinogen,fibrinolytic activity, platelet adhesiveness, plateletfactor 3, factor V, and factor VIII.In the remaining 32 subjects who did not develop pulmonary hypertension there was a significant increase of plasma fibrinogen and fibrinolytic activity only.The above differences between subjects who develop pulmonary hypertension at high altitude and those who do not develop pulmonary hypertension suggest that high altitude pulmonary hyper- tension is of occlusive origin and is dependent on changes in blood coagulation at high altitude.The pathogenesis of high altitude pulmonary hypertension is far from clear.Rotta et al. (I956) found a striking inverse correlation be- tween the degree of arterial oxygen saturation and the level of the mean pulmonary arterial pressure.However, with acetylcholine and oxygen therapy, pulmonary hypertension de- creased only to the extent of I5 to 20 per cent.Evidently, hypoxia does not affect the pulmonary arterial pressure directly to any conspicuous extent.Campos and Iglesias (I957) observed an obvious dilatation of the vascular bed of the lungs.There is also thickening of the muscu- lar layer of the small pulmonary arteries and muscularization of the pulmonary arterioles (Arias-Stella and Saldania, I962).Pen'ialoza et al. (I963) attributed high altitude pulmonary hypertension to increased pulmonary vascular resistance resulting from widespread narrowing of the lumen of the pulmonary blood vessels on account of these changes.However, in our experience with soldiers temporarily posted at high altitudes, who develop pulmonary hypertension and die of it, these changes are not prominent (see below).It seems more likely that these changes are not causal but secondary to long-standing hypertension.The pulmonary blood flow, as indicated by a nor- mal cardiac output, is not increased in pul- monary hypertension.In itself, therefore, an increased pulmonary vascular bed is not con- tributory.In the absence of these changes, dilatation of the vascular bed may be found Received 29 July 197I.in association with an increased pulmonary blood volume, but without pulmonary hyper- tension.Polycythaemia per se does not seem to pre- dispose to pulmonary hypertension.Pulmon- ary hypertension may be present without polycythaemia, or it may persist after the red blood cell count has returned to normal when the individual has returned to sea-level.In our soldiers who are temporarily posted from sea-level to altitudes in the Himalayas, the symptoms of pulmonary hypertension begin after a stay of 5 to 42 months at high altitude.After the initial onset of the disease, periodic returns to sea-level on leave for 2 to 3 months once a year do not alter the picture.The hypertension either persists at sea-level or, if it abates, it reappears within 2 to 3 weeks after the individual returns to high altitude.Though pulmonary vasoconstriction, in- creased pulmonary blood volume, and poly- cythaemia may have some role in the patho- genesis of high altitude pulmonary hyperten- sion, these bases do not explain its slow dis- appearance or persistence when the subjects return to sea-level.In a previous study (Singh et al., i965), based on necropsy findings in high altitude pulmonary hypertension, we reported the presence of numerous occluding fibrin throm- bi in the smaller branches of the pulmonary artery.Several segments of the pulmonary artery and its larger branches showed small but patchy atherosclerotic changes and evi- dence of repeated episodes of thrombosis.A on August 16,