- Email: [email protected]
thrombosis
Thrombosis Research 132 (2013) 635–636
Contents lists available at ScienceDirect
Thrombosis Research journal homepage: www.elsevier.com/locate/thromres
NATF Corner
Tropical hemostasis/thrombosis
In this series of four mini-reviews to be published in Thrombosis Research over the next two issues, we highlight four common tropical diseases affecting the hemostatic system i.e. thalassemia and the hypercoagulable state, snake bites and hemostasis/thrombosis, hemostatic derangement in dengue hemorrhagic fever, and coagulopathy in malaria. With increasing numbers of international travellers from industrialized countries making trips to tropical areas, it is important that details of these diseases be better known throughout the world. Sirachainan - Hypercoagulable State in Thalassemia In this issue of the Journal, Sirachainan begins the series by highlighting the hypercoagulable state in thalassemia. Thalassemia is a hereditary hemolytic anemia characterized by impaired globin chain synthesis. It represents the most common monogenetic disorder worldwide. It occurs most often among people of Southeast Asian, Middle East, Greek, Italian, and African descents. The disorder is characterized by decreased hemoglobin production and red blood cell (RBC) survival resulting from the excess of unaffected globin chain which forms unstable homotetramers, causing RBC damage and severe hemolysis associated with ineffective erythropoiesis and extramedullary hemolysis. The manifestations may begin in the intrauterine period, newborn, infancy, childhood, or adulthood, depending on the severity of the disease. Although subjects with moderate to severe thalassemia are now living longer and have a better quality of life, the presence of a hypercoagulable state from the second decade of life has recently been established [1]. The incidence, evidence, and mechanism of thromboembolism have been explored. The risk factors for thromboembolism in thalassemia are the abnormal red blood cell surface, platelet and endothelial activation, splenectomy, organ dysfunction as a result of iron overload, and underlying inherited thrombophilia. Regular red blood cell transfusion with a pre-transfusion hemoglobin of 10–12 g/dl can reduce the proportion of abnormal red blood cells, suppress excessive erythropoiesis, and decrease the levels of coagulation activation markers [2]. Interestingly, curative stem cell transplantation has also demonstrated the normalization of coagulation markers [3]. McCleary and Kini - Effect of Snake Venom Toxins on the Hemostatic System In the second article, McCleary and Kini review the effect of snake venom toxins on the hemostatic system. The major snake families are the Colubridae, the Elapidae, the Hydrophidae, and the Viperidae. Envenoming snakes cause considerable morbidity and mortality. About five million people are bitten by snakes every year, resulting in up to 2.5 million envenomations, from which there are at least 100,000 deaths 0049-3848/$ – see front matter © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.thromres.2013.09.027
and approximately 300,000 amputations and other permanent disabilities [4]. Most of these occur in Southeast Asia, Africa, and Latin America. Bites by venomous snakes can cause paralysis that may impair breathing; a bleeding disorder that can lead to fatal hemorrhage; or irreversible kidney failure and tissue damage that can cause permanent disability. On the positive side, snake venom toxins can be very useful reagents in the diagnosis of human diseases or as molecular scalpels in physiological studies. Snake venoms are complex mixtures of a number of small polypeptides with diverse pharmacological properties. Snake venom toxins have evolved to be able to disable a prey's physiological systems, including hemostasis. These toxins belong to a diverse array of protein families and can initiate or inhibit multiple stages of the coagulation pathway or platelet aggregation with high specificity. The vast potential source of novel toxins can lead to various new cardiovascular therapeutics and new diagnostic agents. Chuansamrit - Hemostatic Derangement in Dengue Infection In the third review in this series, Chuansamrit describes the hemostatic derangement in dengue infection that is found in tropical and sub-tropical climates worldwide, mostly in urban and semiurban areas. Dengue hemorrhagic fever is the more severe form of dengue infection and is a leading cause of serious illness and death among children in some Asian countries. During the past five decades, the incidence of dengue virus infection has increased 30-fold with geographic expansion to the developed and developing countries all over the world. Some 2.5 billion people – two fifths of the world’s population – are at risk from dengue. It is an emerging mosquito-borne viral infection worldwide. The disease is now endemic in more than 100 countries in Southeast Asia, the Western Pacific, Africa, the Americas, and the Eastern Mediterranean. Although dengue infection is a self-limiting disease in most patients, some individuals with more severe manifestations of shock and hemorrhage called “dengue shock syndrome” by the WHO criteria in 1997 and “severe dengue” by the WHO criteria in 2009, face a high rate of mortality and morbidity. The hallmark finding in patients with dengue hemorrhagic fever is increased vascular permeability resulting in plasma egress from the intravascular compartment. Patients with dengue hemorrhagic fever will exhibit a high hematocrit in addition to thrombocytopenia. The activation of coagulation, fibrinolysis and anticoagulant pathways has been demonstrated with prominent derangement found in patients with the severe form of dengue shock syndrome. Therefore, patients with severe manifestations are at risk of exhibiting excessive bleeding due to endothelial dysfunction, thrombocytopenia and hemostatic derangement. At present, there is no specific treatment for patients with dengue hemorrhagic fever. The awareness with early recognition of hemoconcentration and bleeding manifestations is
636
NATF Corner
essential for a favorable outcome. In patients with underlying hematologic disease such as thalassemia, dengue infection may present with an unusual manifestation of low hematocrit resulting from acute hemolysis instead of the high hematocrit that is commonly found in patients without underlying disease [5]. Packed red cell transfusion is more frequently required compared to those without underlying disease. Moreover, patients with congenital bleeding disorders such as hemophilia may present with excessive bleeding episodes starting from the early febrile stage due to endothelial dysfunction followed by thrombocytopenia in addition to factor VIII or IX deficiency [6]. Factor VIII or IX concentrates combined with platelet concentrates should be administered. Therefore, adequate and appropriate fluid and blood component therapy are essentially required. The more we understand the hemostatic derangement in patients with dengue hemorrhagic fever, the more likely it is that favorable outcomes will be achieved, especially in those patients with severe manifestations. Angchaisuksiri - Coagulopathy in Malaria In the final article of the series, Angchaisuksiri reviews the coagulopathy in malaria, a life-threatening infection caused by Plasmodium parasites that are transmitted to humans through the bites of infected Anopheles mosquitoes. It is the most important parasitic disease of human beings. It is transmitted in 108 countries inhabited by roughly 3 billion people [7]. Although malaria is mainly confined to tropical countries, cases of malaria acquired by international travellers from industrialized countries as well as immigrants from endemic countries have increased worldwide. Therefore, physicians and medical scientists in the developed world should also be aware of this disease. There are five species that cause malaria in human beings. Most cases are caused by either Plasmodium falciparum or Plasmodium vivax, but human infections can also be caused by Plasmodium ovale, Plasmodium malariaec and, in parts of Southeast Asia, the monkey malaria Plasmodium knowlesi [8]. Plasmodium falciparum is the main cause of severe clinical malaria and death. Severe manifestations of Plasmodium falciparum malaria include impaired consciousness (cerebral malaria), respiratory distress, renal failure, hepatic dysfunction, profound anemia, and abnormal bleeding. Many of these complications are believed at least in part to be related to the underlying coagulopathy and microvascular changes in this disease. Malaria is a complex syndrome, with coagulation, inflammation, and parasitized red blood cell sequestration all playing their parts. A basic understanding of how these processes interact to cause the microcirculatory dysfunction and coagulopathy is needed to resolve the controversies regarding adjunct therapy for severe malaria. Novel approaches to malaria, such as therapeutic targeting of tissue factor or
endothelial cells, or drugs based on platelet factor 4 structure could have a significant impact on this important global health problem. We hope that you find the series interesting and informative, and that it increases your interest in these common and important, but often neglected and under-researched, tropical diseases. Conflict of Interest The authors have no conflict of interest to declare. References [1] Eldor A, Rachmilewitz EA. The hypercoagulable state in thalassemia. Blood 2002;99:36–43. [2] Chuncharunee S, Atichartakarn V, Archararit N, Aryurachai K. Correction of coagulation and inflammation activation by chronic blood transfusion in an asplenic patient with haemoglobin E/β-thalassaemia and pulmonary arterial hypertension. Transfus Med 2013;23:276–8. [3] Sirachainan N, Thongsad J, Pakakasama S, Hongeng S, Chuansumrit A, Kadegasem P, et al. Normalized coagulation markers and anticoagulation proteins in children with severe beta-thalassemia disease after stem cell transplantation. Thromb Res 2012;129:765–70. [4] WHO. Snake antivenoms Report 2010. Geneva: World Health Organization; 2010. [5] Chuansumrit A. `Thalassaemia and dengue virus infection. Paediatr Int Child Health 2013;33(1):1–2. http://dx.doi.org/10.1179/2046905512Y.0000000038. [6] Chuansumrit A, Tangnararatchakit K, Sirachainan N, Khositseth A, Kuptanon T, Wanitkun S, et al. Dengue virus infection in hemophilic patients: aggravation of bleeding risk. Haemophilia 2011;17:553–6. [7] White NJ, Pukrittayakamee S, Hien TT, Faiz MA, Mokuolu OA, Dondorp AM. Malaria. Lancet Aug 15 2013. http://dx.doi.org/10.1016/S0140-6736(13)60024-0 [Epub ahead of print]. [8] Kantele A, Jokiranta TS. Review of cases with the emerging fifth human malaria parasite, Plasmodium knowlesi. Clin Infect Dis 2011;52:1356–62.
Pantep Angchaisuksiri1 Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand Corresponding author at: Division of Hematology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Rama VI Road, Bangkok 10400, Thailand. E-mail address: [email protected]. Ampaiwan Chuansumrit2 Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand E-mail address: [email protected].
17 September 2013
1 2
Tel./fax: +66 2 2011796. Tel.: +66 2 2011749; fax: +66 2 2011748.
Contents lists available at ScienceDirect
Thrombosis Research journal homepage: www.elsevier.com/locate/thromres
NATF Corner
Tropical hemostasis/thrombosis
In this series of four mini-reviews to be published in Thrombosis Research over the next two issues, we highlight four common tropical diseases affecting the hemostatic system i.e. thalassemia and the hypercoagulable state, snake bites and hemostasis/thrombosis, hemostatic derangement in dengue hemorrhagic fever, and coagulopathy in malaria. With increasing numbers of international travellers from industrialized countries making trips to tropical areas, it is important that details of these diseases be better known throughout the world. Sirachainan - Hypercoagulable State in Thalassemia In this issue of the Journal, Sirachainan begins the series by highlighting the hypercoagulable state in thalassemia. Thalassemia is a hereditary hemolytic anemia characterized by impaired globin chain synthesis. It represents the most common monogenetic disorder worldwide. It occurs most often among people of Southeast Asian, Middle East, Greek, Italian, and African descents. The disorder is characterized by decreased hemoglobin production and red blood cell (RBC) survival resulting from the excess of unaffected globin chain which forms unstable homotetramers, causing RBC damage and severe hemolysis associated with ineffective erythropoiesis and extramedullary hemolysis. The manifestations may begin in the intrauterine period, newborn, infancy, childhood, or adulthood, depending on the severity of the disease. Although subjects with moderate to severe thalassemia are now living longer and have a better quality of life, the presence of a hypercoagulable state from the second decade of life has recently been established [1]. The incidence, evidence, and mechanism of thromboembolism have been explored. The risk factors for thromboembolism in thalassemia are the abnormal red blood cell surface, platelet and endothelial activation, splenectomy, organ dysfunction as a result of iron overload, and underlying inherited thrombophilia. Regular red blood cell transfusion with a pre-transfusion hemoglobin of 10–12 g/dl can reduce the proportion of abnormal red blood cells, suppress excessive erythropoiesis, and decrease the levels of coagulation activation markers [2]. Interestingly, curative stem cell transplantation has also demonstrated the normalization of coagulation markers [3]. McCleary and Kini - Effect of Snake Venom Toxins on the Hemostatic System In the second article, McCleary and Kini review the effect of snake venom toxins on the hemostatic system. The major snake families are the Colubridae, the Elapidae, the Hydrophidae, and the Viperidae. Envenoming snakes cause considerable morbidity and mortality. About five million people are bitten by snakes every year, resulting in up to 2.5 million envenomations, from which there are at least 100,000 deaths 0049-3848/$ – see front matter © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.thromres.2013.09.027
and approximately 300,000 amputations and other permanent disabilities [4]. Most of these occur in Southeast Asia, Africa, and Latin America. Bites by venomous snakes can cause paralysis that may impair breathing; a bleeding disorder that can lead to fatal hemorrhage; or irreversible kidney failure and tissue damage that can cause permanent disability. On the positive side, snake venom toxins can be very useful reagents in the diagnosis of human diseases or as molecular scalpels in physiological studies. Snake venoms are complex mixtures of a number of small polypeptides with diverse pharmacological properties. Snake venom toxins have evolved to be able to disable a prey's physiological systems, including hemostasis. These toxins belong to a diverse array of protein families and can initiate or inhibit multiple stages of the coagulation pathway or platelet aggregation with high specificity. The vast potential source of novel toxins can lead to various new cardiovascular therapeutics and new diagnostic agents. Chuansamrit - Hemostatic Derangement in Dengue Infection In the third review in this series, Chuansamrit describes the hemostatic derangement in dengue infection that is found in tropical and sub-tropical climates worldwide, mostly in urban and semiurban areas. Dengue hemorrhagic fever is the more severe form of dengue infection and is a leading cause of serious illness and death among children in some Asian countries. During the past five decades, the incidence of dengue virus infection has increased 30-fold with geographic expansion to the developed and developing countries all over the world. Some 2.5 billion people – two fifths of the world’s population – are at risk from dengue. It is an emerging mosquito-borne viral infection worldwide. The disease is now endemic in more than 100 countries in Southeast Asia, the Western Pacific, Africa, the Americas, and the Eastern Mediterranean. Although dengue infection is a self-limiting disease in most patients, some individuals with more severe manifestations of shock and hemorrhage called “dengue shock syndrome” by the WHO criteria in 1997 and “severe dengue” by the WHO criteria in 2009, face a high rate of mortality and morbidity. The hallmark finding in patients with dengue hemorrhagic fever is increased vascular permeability resulting in plasma egress from the intravascular compartment. Patients with dengue hemorrhagic fever will exhibit a high hematocrit in addition to thrombocytopenia. The activation of coagulation, fibrinolysis and anticoagulant pathways has been demonstrated with prominent derangement found in patients with the severe form of dengue shock syndrome. Therefore, patients with severe manifestations are at risk of exhibiting excessive bleeding due to endothelial dysfunction, thrombocytopenia and hemostatic derangement. At present, there is no specific treatment for patients with dengue hemorrhagic fever. The awareness with early recognition of hemoconcentration and bleeding manifestations is
636
NATF Corner
essential for a favorable outcome. In patients with underlying hematologic disease such as thalassemia, dengue infection may present with an unusual manifestation of low hematocrit resulting from acute hemolysis instead of the high hematocrit that is commonly found in patients without underlying disease [5]. Packed red cell transfusion is more frequently required compared to those without underlying disease. Moreover, patients with congenital bleeding disorders such as hemophilia may present with excessive bleeding episodes starting from the early febrile stage due to endothelial dysfunction followed by thrombocytopenia in addition to factor VIII or IX deficiency [6]. Factor VIII or IX concentrates combined with platelet concentrates should be administered. Therefore, adequate and appropriate fluid and blood component therapy are essentially required. The more we understand the hemostatic derangement in patients with dengue hemorrhagic fever, the more likely it is that favorable outcomes will be achieved, especially in those patients with severe manifestations. Angchaisuksiri - Coagulopathy in Malaria In the final article of the series, Angchaisuksiri reviews the coagulopathy in malaria, a life-threatening infection caused by Plasmodium parasites that are transmitted to humans through the bites of infected Anopheles mosquitoes. It is the most important parasitic disease of human beings. It is transmitted in 108 countries inhabited by roughly 3 billion people [7]. Although malaria is mainly confined to tropical countries, cases of malaria acquired by international travellers from industrialized countries as well as immigrants from endemic countries have increased worldwide. Therefore, physicians and medical scientists in the developed world should also be aware of this disease. There are five species that cause malaria in human beings. Most cases are caused by either Plasmodium falciparum or Plasmodium vivax, but human infections can also be caused by Plasmodium ovale, Plasmodium malariaec and, in parts of Southeast Asia, the monkey malaria Plasmodium knowlesi [8]. Plasmodium falciparum is the main cause of severe clinical malaria and death. Severe manifestations of Plasmodium falciparum malaria include impaired consciousness (cerebral malaria), respiratory distress, renal failure, hepatic dysfunction, profound anemia, and abnormal bleeding. Many of these complications are believed at least in part to be related to the underlying coagulopathy and microvascular changes in this disease. Malaria is a complex syndrome, with coagulation, inflammation, and parasitized red blood cell sequestration all playing their parts. A basic understanding of how these processes interact to cause the microcirculatory dysfunction and coagulopathy is needed to resolve the controversies regarding adjunct therapy for severe malaria. Novel approaches to malaria, such as therapeutic targeting of tissue factor or
endothelial cells, or drugs based on platelet factor 4 structure could have a significant impact on this important global health problem. We hope that you find the series interesting and informative, and that it increases your interest in these common and important, but often neglected and under-researched, tropical diseases. Conflict of Interest The authors have no conflict of interest to declare. References [1] Eldor A, Rachmilewitz EA. The hypercoagulable state in thalassemia. Blood 2002;99:36–43. [2] Chuncharunee S, Atichartakarn V, Archararit N, Aryurachai K. Correction of coagulation and inflammation activation by chronic blood transfusion in an asplenic patient with haemoglobin E/β-thalassaemia and pulmonary arterial hypertension. Transfus Med 2013;23:276–8. [3] Sirachainan N, Thongsad J, Pakakasama S, Hongeng S, Chuansumrit A, Kadegasem P, et al. Normalized coagulation markers and anticoagulation proteins in children with severe beta-thalassemia disease after stem cell transplantation. Thromb Res 2012;129:765–70. [4] WHO. Snake antivenoms Report 2010. Geneva: World Health Organization; 2010. [5] Chuansumrit A. `Thalassaemia and dengue virus infection. Paediatr Int Child Health 2013;33(1):1–2. http://dx.doi.org/10.1179/2046905512Y.0000000038. [6] Chuansumrit A, Tangnararatchakit K, Sirachainan N, Khositseth A, Kuptanon T, Wanitkun S, et al. Dengue virus infection in hemophilic patients: aggravation of bleeding risk. Haemophilia 2011;17:553–6. [7] White NJ, Pukrittayakamee S, Hien TT, Faiz MA, Mokuolu OA, Dondorp AM. Malaria. Lancet Aug 15 2013. http://dx.doi.org/10.1016/S0140-6736(13)60024-0 [Epub ahead of print]. [8] Kantele A, Jokiranta TS. Review of cases with the emerging fifth human malaria parasite, Plasmodium knowlesi. Clin Infect Dis 2011;52:1356–62.
Pantep Angchaisuksiri1 Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand Corresponding author at: Division of Hematology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Rama VI Road, Bangkok 10400, Thailand. E-mail address: [email protected]. Ampaiwan Chuansumrit2 Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand E-mail address: [email protected].
17 September 2013
1 2
Tel./fax: +66 2 2011796. Tel.: +66 2 2011749; fax: +66 2 2011748.