Pamei Brainy
CIHSR Chümoukedima
Dengue is a viral fever caused by Aedes species mosquito-borne disease caused by any one of four closely related dengue viruses. These viruses are related to the viruses that cause West Nile infection and yellow fever. Dengue fever has emerged as a major public health problem especially in tropical and subtropical regions across the world including Dimapur, Nagaland and also cause global public health problem in recent years. The clinical spectrum of the disease ranges from dengue fever to dengue hemorrhagic fever and dengue shock syndrome (consequence of severe bleeding).The disease is characterized by increased capillary permeability, thrombocytopenia and coagulopathy. Thrombocytopenia (low in platelet count) is the hallmark of the dengue and prophylactic (a medicine or course of action used to prevent disease) platelet transfusion is the one of the treatment to increase circulating platelet count. Thrombocytopenia with hemorrhagic manifestations indicates for platelet transfusions. In patients with dengue hemorrhagic fever or dengue shock syndrome, the duration of shock is the main risk factor for severe bleeding. The early recognition and prevention of shock is the key to treatment. Serial monitoring of hematocrit, platelet count along with judicious intravenous therapy reduces the use of blood and blood products and shortens hospital stay. But, there is lack of evidence-based guidelines for transfusion support in patients with dengue fever in majority of the countries including India which contributes to inappropriate use of blood components. Thus, Blood Centers constantly face the challenge of inventory management during such outbreak, so want to highlight the role of platelets and other blood components in the management of dengue.
Various grades of bleeding manifestations have been defined by World Health Organization (WHO) but, there are few guidelines as to the transfusion management of patients with dengue fever. Prophylactic platelet transfusions are given in dengue fever with thrombocytopenia to prevent bleeding and hemorrhagic complications. Although the use of prophylactic platelet transfusions is increasing in countries where dengue is endemic, it is associated with risks, burden to search potential healthy blood donors and has involve with financial implications. The decision to transfuse platelets is based on several factors including estimation of platelet count and platelet function, the root cause of thrombocytopenia, the status of coagulation system, the presence or likelihood / tendency of bleeding and the risks of transfusion. Other transfusion strategies include blood transfusion for severe bleeding manifestations, Fresh Frozen Plasma (FFP) and cryoprecipitate for patients with deranged coagulation profile Prothrombin Time (PT), Activated Partial thromboplastin Time (APTT), fribrinogen and D-dimer. Prophylactic platelet transfusions are defined as platelet transfusions given in the absence of clinical bleeding, in contrast to therapeutic platelet transfusions given to patients with clinical bleeding. The British Committee for standardization in hematology guidelines on platelet transfusion recommend a trigger of 10,000/μl for stable thrombocytopenic patients without additional risk factors for bleeding. Similar guidelines have been issued by the Directorate of national vector borne diseases control program, Government of India.
Guidelines in platelet transfusion in dengue patient:
1. Packed red cells – loss of blood (overt blood)- 10% or more of total blood volume. Refractory shock despite adequate fluid administration and declining haematocrit. Replacement volume should be 10ml/ KG body weight at a time and coagulogram should be done. If fluid overload is present packed red cells (PRBC) should be given.
2. Platelets – in general there is no need to give prophylactic even at <20000 /cumm. Prophylactic platelet transfusion may be given at level of < 10000/cumm in absences of bleeding manifestation. Prolong shock with coagulopathy and abnormal coagulogram. In case of systemic massive bleeding platelet transfusion may be needed in addition to red cells transfusion.
3. Fresh frozen plasma (FFP)/cryoprecipitate – Coagulopathy with bleeding. Patient’s clinical condition may be considered or as per the advice of the physician. Recombinant factor VIIa may be given in severe uncontrolled bleeding as FVIIa enhances thrombin generation. It also increases the activity and function of patients and transfused platelets by direct activation of factor X on platelet surface.
Globally, Blood transfusion services (Blood Center) faces challenges year after year during dengue outbreaks due to lack of evidence based guidelines for clinical use of blood and blood components. And the demand for platelets and FFP are increasing due to more number of cases with dengue hemorrhagic fever and dengue shock syndrome. Transfusion of blood components is associated with many adverse effects. The major risks associated with transfusion of platelets include febrile non hemolytic transfusion reactions, allergic reactions, bacterial sepsis, transfusion related acute lung injury (TRALI), alloimmunization (antibodies /immune response to foreign antigens after exposure to genetically different cells or tissues), and platelet refractoriness, pulmonary edema and transfusion transmitted infections. Hence, it is prudent to consider transfusion only if the benefits outweigh the accompanying risks of transfusion.
Apart from the dengue fever, according to "Evaluation and management of disseminated intravascular coagulation (DIC) in adults", section on 'Treatment' and "Spontaneous intracerebral hemorrhage: Acute treatment and prognosis" – Actively bleeding patients with thrombocytopenia should be transfused with platelets immediately to keep platelet counts >50,000/microL in most bleeding situations including disseminated intravascular coagulation (DIC), and >100,000/microL if there is central nervous system bleeding.
Typical recommended platelet count thresholds used for some common procedures can be listed - Platelet transfusion may be considered when the patient platelet count is below the threshold for the corresponding procedure:
• Neurosurgery or ocular surgery – <100,000/microL
• Most other major surgery – <50,000/microL
• Endoscopic procedures – <50,000/microL for therapeutic procedures; 20,000/microL for low risk diagnostic procedures (see "Gastrointestinal endoscopy in patients with disorders of hemostasis")
• Bronchoscopy with bronchoalveolar lavage (BAL) – <20,000 to 30,000/microL
• Central line placement – <20,000/microL
• Lumbar puncture – <10,000 to 20,000/microL in patients with hematologic malignancies and <40,000 to 50,000 in patients without hematologic malignancies; lower thresholds may be used in patients with immune thrombocytopenia (ITP)
• Neuraxial analgesia/anesthesia – <80,000/microL According to
• Bone marrow aspiration/biopsy – <20,000/microL
To prevention of spontaneous bleeding — Prophylactic platelet transfusion to prevent spontaneous bleeding in most afebrile patients with platelet counts <10,000/microL due to bone marrow suppression.
For patients with fever, infection, or inflammation, we generally transfuse at a platelet count ≤15,000 to 20,000/microL due to the increased risk of bleeding
• Acute Promyelocytic Leukemia (APL) – Patients with APL differ from other patients with AML because they often have an associated severe coagulopathy that puts them at high risk for disseminated intravascular coagulation and bleeding. Prophylactically transfuse the patients at a platelet count of ≤30,000 to 50,000/microL. To treat any sign of bleeding, especially central nervous system bleeding, with immediate platelet transfusion and adults with ALL at a threshold platelet count of 10,000/microL. Cancer chemotherapy often makes patients thrombocytopenic from bone marrow suppression.
Individuals with acute ITP (common in children below 4 years) and chronic ITP (usually seen in adult female population) produce antiplatelet antibodies that destroy circulating platelets and significant amount megakaryocytes in the bone marrow. Circulating platelets in patients in ITP tends to be highly functional, and platelet counts tend to be well and patient are asymtomatic if the platelet count above 30,000/microL. Bleeding is rare even in patients with severe thrombocytopenia (platelet count <30,000/microL. Liver diseases and disseminated intravascular coagulation (DIC) which is cause by inflammation from an infection, injury or illness are two cases that can cause a complex mixture of abnormalities with procoagulant and anticoagulant effects, along with thrombocytopenia, patients with either of these disorders are at risk for both thrombosis and bleeding. There is no evidence to support the administration of platelets in such patients if they are not bleeding. However, in such cases platelet transfusion is justified in patients who have serious bleeding and are at high risk for bleeding (eg, after surgery) or require invasive procedures.
Patients with massive blood loss from surgery or trauma are transfused with red blood cells (RBCs), resulting in partial replacement of the blood volume with a product lacking platelets and clotting factors. In such situation transfusion with RBCs, fresh frozen plasma (FFP), and platelet units in a 1:1:1 ratio. As an example- a patient transfused with 5 units of RBCs would received platelet product (containing four to five platelet concentrates) or one apheresis unit and five units of FFP.
The major disadvantage of random platelets is recipient exposure to multiple donors in a single transfusion and the increased work of bacterial testing. In addition, it is more labor intensive and time consuming for platelet separation. Both random platelets and apheresis platelets contain some WBCs that were collected along with the platelets. These WBCs can cause febrile nonhemolytic transfusion reactions (FNHTR), alloimmunization, or transfusion-associated graft-versus-host disease (TA-GVHD) in some patients. "Immunologic transfusion reactions", section on 'Febrile nonhemolytic transfusion reactions' and "Transfusion-associated graft-versus-host disease". Platelet products are suspended either in plasma or in platelet additive solution, which reduces the plasma volume by approximately one-third. Because of their plasma content, transfused platelets can cause adverse reactions including transfusion-related to acute lung injury (TRALI) and anaphylaxis (type-I hypersensitivity reaction). "Immunologic transfusion reactions", section on 'Anaphylactic transfusion reactions' and "Transfusion-related acute lung injury (TRALI)". Transfusion-associated graft-versus-host disease is a phenomenon in which donor T cells, responding to proteins on host cells, proliferate and target host organs, primarily the skin, liver, intestinal tract and bone marrow. TA-GVHD risk can be reduced greatly by not transfusing genetically related donors blood such as siblings, parents, cousins and close relatives.
Platelet can be transfuse to all types of blood group as blood type matching between donors and patient does not matter when transfusing platelets. Platelets concentrates can contain a small number of RBCs that express Rh antigens on their surface (platelets do not express Rh antigens). The small numbers of RBCs in apheresis platelet and random donor platelets pose an extremely low, but non-zero risk of Rh alloimmunization in most patients. However, transfusion medicine services avoid giving platelets from RhD-positive donors to RhD-negative females of childbearing potential because of the potential risk of RhDalloimmunization and subsequent hemolytic disease of the fetus and newborn (HDFN).
Platelets are routinely stored at room temperature, because cold induces clustering of von Willebrand factor (WVF) receptors on the platelet surface and morphological changes of the platelets, leading to enhanced clearance by hepatic macrophages and reduced platelet survival in the recipient. All the blood cells are more metabolically active at room temperature, platelets are stored in bags that allow oxygen and carbon dioxide gas exchange, citrate prevent clotting and maintain proper pH .The risk of bacterial infection from platelets increases with storage duration. The shelf-life of platelets stored at room temperature is generally only five days, which are counted starting from midnight on the day of collection. This short shelf-life contributes to the potential for low platelet inventory and platelet shortages.
The Blood transfusion services constantly face challenges during dengue outbreaks due to lack of evidence based guidelines for clinical use of blood and blood components. The demand for platelets and FFP is increasing due to more number of cases with dengue hemorrhagic fever and dengue shock syndrome. Transfusion of blood components is associated with many adverse effects. The major risks associated with transfusion of platelets include febrile non hemolytic transfusion reactions, allergic reactions, bacterial sepsis, transfusion related acute lung injury, alloimmunization, and platelet refractoriness, pulmonary edema and transfusion transmitted infections. Hence, it is prudent to consider transfusion only if the benefits outweigh the accompanying risks of transfusion.
Inappropriate use of blood and blood components during dengue fever outbreaks essentially depletes the inventory of blood centers. And further, lack of knowledge, absence of evidence based guidelines and panic like situation leads to flooding of transfusion services with blood and component requests. A proper management system with donor registries, guidelines and regular awareness programs for the potential healthy donors in communities, colleges, institutions and offices can go along for the better management of dengue outbreaks and other diseases which require platelets and other blood products.
The writer is an Asst Professor at the North East Regional Multidisciplinary Paramedical Institute (NERMPI) & Deputy Technical Supervisor CIHSR Blood Centre.
