Venous thrombosis at altitude presents with distinct biochemical profiles: a comparative study from the Himalayas to the plains

Prabhakar, Amit; Chatterjee, Tathagata; Bajaj, Nitin; Tyagi, Tarun; Sahu, Abhiram; Gupta, Neha; Kumari, Babita; Nair, Velu; Kumar, Bhuvnesh; Ashraf, Mohammad Zahid

doi:10.1182/bloodadvances.2018024554

Cited by 30 publications

(23 citation statements)

References 64 publications

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“…It has been proposed that disruption of the coagulation-fibrinolytic axis resulting in excessive fibrin formation and deposition might underlie the increased thrombotic risk associated with high altitude and chronic mountain sickness (Kotwal et al, 2007;Mannucci et al, 2002;Prabhakar et al, 2019;Singh & Chohan, 1972) F I G U R E 1 Plasma von Willebrand factor (vWf; a), factor VII (b), factor VII (c) and factor X (d) in Andean highlanders without and with excessive erythrocytosis. The mean value is denoted with a horizontal line (Junker et al, 1997;Kleinegris et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Specific markers of the blood coagulation cascade, fibrinolytic system and fibrin formation were remarkably similar between Andean highlanders with EE and those without EE. It has been proposed that disruption of the coagulation–fibrinolytic axis resulting in excessive fibrin formation and deposition might underlie the increased thrombotic risk associated with high altitude and chronic mountain sickness (Kotwal et al., 2007; Mannucci et al., 2002; Prabhakar et al., 2019; Singh & Chohan, 1972). However, in the present study, otherwise healthy Andean highlander men with EE did not display prothrombotic alterations in blood coagulation and fibrinolytic factors, suggesting that neither coagulation nor fibrinolytic dysfunction contributes to the increased thrombotic risk with high‐altitude EE.…”

Section: Discussionmentioning

confidence: 99%

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Global REACH 2018: Influence of excessive erythrocytosis on coagulation and fibrinolytic factors in Andean highlanders

DeSouza

Brewster

Bain

et al. 2021

Experimental Physiology

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Increased coagulation and reduced fibrinolysis are central factors underlying thrombotic risk and events. High altitude-induced excessive erythrocytosis (EE) is prevalent in Andean highlanders, contributing to increased cardiovascular risk. Disruption in the coagulation-fibrinolytic axis resulting in uncontrolled fibrin deposition might underlie the increased thrombotic risk associated with highaltitude EE. The experimental aim of this study was to determine whether EE is associated with a prothrombotic blood coagulation and fibrinolytic profile in Andean highlanders. Plasma coagulation factors (von Willebrand factor and factors VII, VIII and X), fibrinolytic factors [tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1)] and D-dimer levels were determined in 26 male residents

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Global REACH 2018: Influence of excessive erythrocytosis on coagulation and fibrinolytic factors in Andean highlanders

DeSouza

Brewster

Bain

et al. 2021

Experimental Physiology

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“…Though Virchow's triad describing hypercoagulability, hemodynamic changes and endothelial dysfunction contributes to the thrombus formation along with plethora of other independent risk factors such as infection (Esmon, 2009). Lately, exposure to high-altitude (HA) has also been associated with the increased frequency of occurrence and probability of thromboembolic complications (Prabhakar et al, 2019). Perhaps the extreme condition at HA such as severe dehydration, hemoconcentration, hypobaric hypoxia and low temperature would affirm the happening of these events (Gupta and Ashraf, 2012).…”

Section: Introductionmentioning

confidence: 99%

Understanding Inflammatory Responses in the Manifestation of Prothrombotic Phenotypes

Chanchal

Mishra

Singh

et al. 2020

Front. Cell Dev. Biol.

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Inflammasome complex is a multimeric protein comprising of upstream sensor protein of nucleotide-binding oligomerization domain (NOD)-like receptor family. It has an adaptor protein apoptosis-associated speck-like protein and downstream effector cysteine protease procaspase-1. Activation of inflammasome complex is body's innate response to pathogen attack but its abnormal activation results in many inflammatory and cardiovascular disorders including thrombosis. It has displayed a prominent role in the clot formation advocating an interplay between inflammation and coagulation cascades. Therefore, elucidation of inflammasome and its molecular mechanisms in the manifestation of prothrombotic phenotypes becomes pertinent. Thrombosis is the formation and propagation of blood clot in the arterial or venous system due to several interactions of vascular and immune factors. It is a prevalent pathology underlying disorders like venous thromboembolism, stroke and acute coronary syndrome; thus, making thrombosis, a major contributor to the global disease burden. Recently studies have established a strong connection of inflammatory processes with this blood coagulation disorder. The hemostatic balance in thrombosis gets altered by the inflammatory mechanisms resulting in endothelial and platelet activation that subsequently increases secretion of several prothrombotic and antifibrinolytic factors. The upregulation of these factors is the critical event in the pathogenesis of thrombosis. Among various inflammasome, nucleotide-binding domain, leucine-richcontaining family, pyrin domain containing 3 (NLRP3) is one of the best-studied sterile inflammasome strengthening a link between inflammation and coagulation in thrombosis. NLRP3 activation results in the catalytic conversion of procaspase-1 to active caspase-1, which facilitate the maturation of interleukin-1β (IL-1β) and interleukin-18. These cytokines are responsible for immune cells activation critical for immune responses. These responses further results in endothelial and platelet activation and aggregation. However, the exact molecular mechanism related to the pathogenesis of thrombosis is still elusive. There have been several reports that demonstrate Tissue factor (TF)-mediated signaling in the production of pro-inflammatory cytokines enhancing inflammation by activating protease-activated receptors on various cells,

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“…High values of soluble P-selectin remain in the blood plasma of patients after VTE, residing at more than 3000 m above the sea level, and of patients with atherothrombotic vascular conditions, which indicates constant platelet activation [ 100 , 101 ]. Enhanced levels of soluble CD40L, P-selectin, and platelet factor-4 (PF-4) reflect platelet reactivity in high altitude hypoxia and could play a significant role in thrombotic complications [ 102 ].…”

Section: The Role Of Platelets In Pa Thrombosismentioning

confidence: 99%

Pulmonary Artery Thrombosis: A Diagnosis That Strives for Its Independence

Porembskaya

Toropova

Tomson

et al. 2020

IJMS

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According to a widespread theory, thrombotic masses are not formed in the pulmonary artery (PA) but result from migration of blood clots from the venous system. This concept has prevailed in clinical practice for more than a century. However, a new technologic era has brought forth more diagnostic possibilities, and it has been shown that thrombotic masses in the PA could, in many cases, be found without any obvious source of emboli. Chronic obstructive pulmonary disease, asthma, sickle cell anemia, emergency and elective surgery, viral pneumonia, and other conditions could be complicated by PA thrombosis development without concomitant deep vein thrombosis (DVT). Different pathologies have different causes for local PA thrombotic process. As evidenced by experimental results and clinical observations, endothelial and platelet activation are the crucial mechanisms of this process. Endothelial dysfunction can impair antithrombotic function of the arterial wall through downregulation of endothelial nitric oxide synthase (eNOS) or via stimulation of adhesion receptor expression. Hypoxia, proinflammatory cytokines, or genetic mutations may underlie the procoagulant phenotype of the PA endothelium. Both endotheliocytes and platelets could be activated by protease mediated receptor (PAR)- and receptors for advanced glycation end (RAGE)-dependent mechanisms. Hypoxia, in particular induced by high altitudes, could play a role in thrombotic complications as a trigger of platelet activity. In this review, we discuss potential mechanisms of PA thrombosis in situ.

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Venous thrombosis at altitude presents with distinct biochemical profiles: a comparative study from the Himalayas to the plains

Abstract: Key PointsHA exposure alters hemostatic systems and contributes to the onset of VTE at a younger age. Aggravated disruption of coagulation, platelet, and endothelial function differentiates HA-induced VTE from VTE on the plains.

Cited by 30 publications

References 64 publications

Global REACH 2018: Influence of excessive erythrocytosis on coagulation and fibrinolytic factors in Andean highlanders

Global REACH 2018: Influence of excessive erythrocytosis on coagulation and fibrinolytic factors in Andean highlanders

Understanding Inflammatory Responses in the Manifestation of Prothrombotic Phenotypes

Pulmonary Artery Thrombosis: A Diagnosis That Strives for Its Independence

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