L Pantanowitz. Mechanisms of Thrombocytopenia in Tick-Borne Diseases. The Internet Journal of Infectious Diseases. 2002 Volume 2 Number 2.
Thrombocytopenia is a common manifestation of all tick-borne diseases. Low platelet numbers contribute significantly towards the morbidity and mortality of infection. However, the pathogenesis of thrombocytopenia in many of the tick-borne diseases is poorly understood. Quantitative changes in platelet counts associated with infection may result from decreased marrow production, hypersplenism, consumption due to widespread endothelial damage or disseminated intravascular coagulation, as well as immune-mediated platelet destruction. Infection-induced thrombocytopenia may infrequently be associated with serious thrombosis. Direct infection of platelets by selected tick-borne pathogens also facilitates their dissemination within the host. This article reviews the mechanisms of thrombocytopenia associated with tick-borne infections, and discusses the therapeutic options available for managing this potentially fatal complication.
Ticks are hematophagous parasites that are worldwide in distribution. They are efficient transmitters of viral, bacterial, rickettsial and protozoal pathogens. Nearly all of the tick-borne infections in mammalian hosts may have, as a component of the clinical syndrome, thrombocytopenia. Quantitative changes in platelet counts may result from decreased platelet production, hypersplenism and non-immune as well as immune-mediated destruction or consumption of platelets. Thrombocytopenia usually presents with bleeding, characteristically mucosal and cutaneous. Bleeding into the skin is evident as petechiae or superficial ecchymoses. Most patients with Rocky Mountain Spotted Fever (RMSF), for example, develop a maculopapular rash on the third day of illness, which later evolves to become petechial. Heavy gastrointestinal bleeding and bleeding into the central nervous system may be life-threatening manifestations of thrombocytopenia. Profuse bleeding and ecchymoses with hypovolemic shock are features commonly found in Crimean-Congo Hemorrhagic Fever (CCHF) viral infections (Zaki and Peters 1997), and occasionally in babesiosis (Mintz
Decreased Platelet Production
Morulae and granulomas may be found in the bone marrow of pancytopenic patients with ehrlichiosis (Dumler
The spleen plays a pivotal role in host defense by clearing microorganisms and antibody-coated cells. It is also important for antibody synthesis. Furthermore, it acts as a reservoir for platelets, containing a large exchangeable platelet pool. In some animals, like dogs and cats, the spleen provides an important reservoir for erythrocytes. Splenomegaly, which is associated with many of the tick-borne diseases, causes increased platelet sequestration and destruction by splenic macrophages. Whole-body scans of dogs infected with
Non-immune Platelet Consumption
Thrombocytopenia may occur as a consequence of vascular damage, with widespread deposition of platelets on damaged endothelial surfaces (Silverman 1986; Elghetany and Walker 1999). Injured endothelium may become denuded, exposing thrombogenic subendothelium. The endothelial cell is the primary target in rickettsial infections. Platelet adhesion to injured endothelium is the major mechanism of thrombocytopenia in the spotted fever group of diseases (Rao
Thrombotic thrombocytopenic purpura (TTP) is a potentially fatal disease characterized by widespread thrombi in the microcirculation. The hallmarks of TTP are thrombocytopenia, microangiopathic hemolytic anemia (with fragmented erythrocytes seen on a blood smear), fluctuating neurologic abnormalities, fever, and renal disease. The pathologic feature characteristic of TTP is microthrombi, composed of platelets and fibrin, which occlude arterioles and capillaries in multiple organs. Unlike DIC, however, localized fibrinolytic activity is absent in vessels occluded by these microthrombi, and the coagulation parameters are rarely affected. TTP is often associated with the excessive release of unusually large von Willebrand factor (vWF) multimers, from disturbed systemic endothelial cells. Patients with tick-borne diseases, such as RMSF (Turner
Direct Infection of Platelets
Direct infection of platelets, as occurs with
Immune-mediated Platelet Destruction
Autoimmunity is a phenomenon observed in many tick-borne diseases, and may contribute to thrombocytopenia in these cases. Autoreactive antibodies that bind to platelets shorten their life span, due to the clearance of antibody-coated platelets by the reticuloendothelial system. The incidence of autoimmune disorders in patients with Q fever (Levy
Thrombocytopenia due to tick-borne infection is likely to be of multifactorial etiology. In many of these infections, however, the actual mechanism of thrombocytopenia still remains unknown. Iatrogenic causes in some cases, such as drugs, should not be overlooked. Low platelet numbers in infected individuals may not only manifest with increased bleeding, but may herald more widespread life-threatening microthrombus formation. In addition to quantitative platelet disorders, qualitative defects may also be present. For example, inhibition of platelet migration has been induced by serum from
Therapy for thrombocytopenia requires treatment or removal of the underlying infection, in addition to maintenance of platelet counts and hemostatic function. However, identification and correction of a specific tick-borne infection is only possible if the infection is considered in the differential diagnosis of thrombocytopenia. Rapid treatment of the underlying infection should result in normalization of platelet counts. Ehrlichia, bartonella and RMSF should also be excluded in cases presenting with a clinical picture resembling TTP, particularly in those patients that prove difficult to manage, and in regions where the incidence of tick-borne illness is high. The efficacy of platelet transfusions in many of the tick-borne diseases is unclear and anecdotal (Van Eeden