High-Altitude Polycythemia

Winslow, Robert M.

doi:10.1007/978-1-4614-7525-5_15

Cited by 11 publications

(10 citation statements)

References 30 publications

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“…Hematocrit values of 0.72 to 0.91 have been reported in highaltitude inhabitants, 21,22 erythrocytosis from congenital heart disease, 23 neonatal erythrocytosis, 24 polycythemia vera, 18 and Chuvash polycythemia. 25 From the published literature a hematocrit value of 0.85 was expected to be associated with thrombosis and embolization.…”

Section: Discussionmentioning

confidence: 99%

Hemostasis and coagulation at a hematocrit level of 0.85: functional consequences of erythrocytosis

Shibata¹,

Hasegawa²,

Siemens³

et al. 2003

Blood

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We have generated a transgenic mouse line that reaches a hematocrit concentration of 0.85 due to constitutive overexpression of human erythropoietin in an oxygen-independent manner. Unexpectedly, this excessive erythrocytosis did not lead to thrombembolic complications in all investigated organs at any age. Thus, we investigated the mechanisms preventing thrombembolism in this mouse model. Blood analysis revealed an age-dependent elevation of reticulocyte numbers and a marked thrombocytopenia that matched the reduced megakaryocyte numbers in the bone marrow. However, platelet counts were not different from wild-type controls, when calculations were based on the distribution (eg, plasma) volume, thereby explaining why thrombopoietin levels did not increase in transgenic mice. Nevertheless, bleeding time was significantly increased in transgenic animals. A longitudinal investigation using computerized thromboelastography revealed that thrombus formation was reduced with increasing age from 1 to 8 months in transgenic animals. We observed that increasing erythrocyte concentrations inhibited profoundly and reversibly thrombus formation and prolonged the time of clot development, most likely due to mechanical interference of red blood cells with clot-forming platelets. Transgenic animals showed increased nitric oxide levels in the blood that could inhibit vasoconstriction and platelet activation. Finally, we observed that plasmatic coagulation activity in transgenic animals was significantly decreased. Taken together, our findings suggest that prevention of thrombembolic disease in these erythrocytotic transgenic mice was due to functional consequences inherent to increased erythrocyte concentrations and a reduction of plasmatic coagulation activity, the cause of which remains to be elucidated. (Blood. 2003;101:4416-4422)

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Section: Discussionmentioning

confidence: 99%

Hemostasis and coagulation at a hematocrit level of 0.85: functional consequences of erythrocytosis

Shibata¹,

Hasegawa²,

Siemens³

et al. 2003

Blood

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“…A previous study reported that digestive symptoms such as epigastric pain, dyspepsia, anorexia, vomiting and diarrhea, which frequently occur in patients with HAPC, may be eliminated in 89-100% of cases (4). Gastric mucosal lesions (GML) are a common complication of HAPC.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of apoptosis involved in gastric mucosal lesions in Tibetans with high-altitude polycythemia

Li¹,

Gesang²,

Cai³

2017

Experimental and Therapeutic Medicine

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“…For example, acute high altitude hypoxia combined with hyperventilation-induced alkalosis shifts the ODC to the left. An increase of red cell 2,3-DPG may, however, oppose this effect and return the ODC to its normal position (4). Modulations of 2,3-DPG concentrations may also occur during lack of oxygen due to congenital cardiac problems, anemia and chronically reduced cardiac output.…”

Section: Introductionmentioning

confidence: 99%

The effects of 2,3-diphosphoglycerate, adenosine triphosphate, and glycosylated hemoglobin on the hemoglobin-oxygen affinity of diabetic patients

Castilho

Glass

Manço

2003

Braz J Med Biol Res

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The position of the oxygen dissociation curve (ODC) is modulated by 2,3-diphosphoglycerate (2,3-DPG). Decreases in 2,3-DPG concentration within the red cell shift the curve to the left, whereas increases in concentration cause a shift to the right of the ODC. Some earlier studies on diabetic patients have reported that insulin treatment may reduce the red cell concentrations of 2,3-DPG, causing a shift of the ODC to the left, but the reports are contradictory. Three groups were compared in the present study: 1) nondiabetic control individuals (N = 19); 2) insulin-dependent diabetes mellitus (IDDM) patients (on insulin treatment) (N = 19); 3) non-insulin-dependent diabetes mellitus (NIDDM) patients using oral hypoglycemic agents and no insulin treatment (N = 22). The overall position of the ODC was the same for the three groups despite an increase of the glycosylated hemoglobin fraction that was expected to shift the ODC to the left in both groups of diabetic patients (HbA 1c : control, 4.6%; IDDM, 10.5%; NIDDM, 9.0%). In IDDM patients, the effect of the glycosylated hemoglobin fraction on the position of the ODC appeared to be counterbalanced by small though statistically significant increases in 2,3-DPG concentration from 2.05 (control) to 2.45 µmol/ml blood (IDDM). Though not statistically significant, an increase of 2,3-DPG also occurred in NIDDM patients, while red cell ATP levels were the same for all groups. The positions of the ODC were the same for control subjects, IDDM and NIDDM patients. Thus, the PO 2 at 50% hemoglobinoxygen saturation was 26.8, 28.2 and 28.5 mmHg for control, IDDM and NIDDM, respectively. In conclusion, our data question the idea of adverse side effects of insulin treatment on oxygen transport. In other words, the shift to the left reported by others to be caused by insulin treatment was not detected.

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High-Altitude Polycythemia

Cited by 11 publications

References 30 publications

Hemostasis and coagulation at a hematocrit level of 0.85: functional consequences of erythrocytosis

Hemostasis and coagulation at a hematocrit level of 0.85: functional consequences of erythrocytosis

Mechanism of apoptosis involved in gastric mucosal lesions in Tibetans with high-altitude polycythemia

The effects of 2,3-diphosphoglycerate, adenosine triphosphate, and glycosylated hemoglobin on the hemoglobin-oxygen affinity of diabetic patients

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