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Platelet Dysfunction in Acute Leukemias and Myelodysplastic Syndromes


Department of Hematology, Emergency Universitary Hospital Bucharest, Romania, 2 Carol Davila University of Medicine and Pharmacy, Bucharest

The hemorrhagic and thrombotic diathesis represents a frequent complication in myelodysplastic syndromes (MDS) and in acute leukemias. They are correlated with the number of the platelets, but also with their qualitative disorders, such as membrane glycoprotein changes. The latter are revealed by many platelet studies including flow-cytometry and comprise modified activation, secretion and aggregation patterns. Key words: myelodysplastic syndromes, thrombosis, hemorrhage.

The clonal stem cell disorders, such as myelodysplastic syndromes and acute leukemias, are associated with qualitative and quantitative disorders of the platelets [1]. These dysfunctions are thought to cause bleeding and thrombotic complications. This is the reason why hemorrhagic and thrombotic events occur quite frequently in patients suffering of myelodysplastic syndromes and acute leukemias and are also considered important causes of morbidity and mortality [1]. The qualitative defects of the platelets, together with their quantitative alterations as thrombocytopenia, produce important disorders of hemostasis. The spectrum of platelets disorders and their clinical picture is different in MDS and acute leukemias. The thrombotic risk is increasing with age, a previous thrombosis history and the occurrence of general associated risk factors such as hypercholesterolemia, smoking, diabetes mellitus, arterial hypertension, etc.

The bleeding tendency in AML patients is the result of the platelet production defect leading to thrombocytopenia, and also of the qualitative changes of the platelets. In theses diseases, the thrombocytopenia is the most frequent cause of bleeding tendency. The relationship between bleeding and thrombocytoROM. J. INTERN. MED., 2011, 49, 1, 9396

penia was very well studied, and the bleeding is considered a frequent complication of induction chemotherapy or stem-cell transplant in acute myeloid leukemia [2]. The platelet concentrate transfusion decreases the bleeding risk in AML patients, but despite this fact, the risk of an important hemorrhagic complication still exists. The data reveals that important clinical hemorrhage occurs in 2030% of AML thrombocytopenic patients (there are nor included APL patients) and 3458% of allogeneic SCT patients [3][4]. It was suggested that additional risk factors are involved in the bleeding tendency, including fever, sepsis, infections, anticoagulant therapy, drugs, coagulation anomalies, platelets function defects, anatomic anomalies, uremia, hypoalbuminemia, recent bone marrow transplant, recent hemorrhage, low hematocrit [58]. Data about the independent predictive role of these factors of bleeding risk in acute leukemia patients are very poor, and also about the estimation of severity of the bleeding. In thrombocytopenic patients, the increase of platelets number was correlated with the decrease of all kinds of bleeding (mild, clinical significant and severe). In 1962, Gaydos et al. [9] were the first to prove the correlation between bleeding and the number of platelets in acute leukemia patients. They have shown a linear relationship between these. The bleeding complications could also occur in patients with a normal platelet number, because of platelets qualitative dysfunctions.


Ana Maria Vldreanu et al.

The acquired changes of the platelets functions associated with bleeding diathesis are more frequent in acute myeloblastic leukemia, including acute myelomonocytic leukemia, acute lymphoblastic leukemia, hairy-cell leukemia and myelodysplastic syndrome [10]. The most frequent platelet disorders are: inadequate platelet aggregation to ADP, epinephrine, collagen, low nucleotides secretion, low secretion of serotonin, decrease of thromboxane production and low PDGF and beta-thromboglobulin production [1114].

In AML and MDS, the megakaryocytes are dysplastic (Fig. 1), and this is reflected in platelets morphology and function. The platelets could be large and morphologically abnormal. Ultrastructural studies have shown the decrease of microtubuli, low number and abnormal sizes of dense granules. In AML we can discover abnormal megakaryopoiesis and hypogranular megakaryocytes, indicating a platelet production defect. In Table I there are shown the main receptors of platelets and their role in platelet function.

Figure 1. Abnormal megakaryopoiesis (May Grunwald Giemsa stains: 20x) Clinic of Hematology Universitary Emergency Hospital Bucharest Romania. Table I Platelet glicoproteins characteristics. Glycoprotein GPIIb/IIIa (alphaIIb beta3; CD41/CD61) GP Ia-IIa (VLA-2; alpha2 beta1 ; CD49b/CD29) GP Ic-IIa (alpha5 beta1; CD49e/CD29) GP Ic-IIa (VLA-6; alpha6 beta1; CD49f/CD29) alphav beta3 (CD51/CD61) GP Ib-IX (CD42) Ib (alpha and beta) IX (one chain) 170,000 17,000-22,000 Subunits IIb (alpha and beta) IIIa (one chain) IIa (one chain) Ia (one chain) Ic (alpha and beta) IIa (one chain) Ic (alpha and beta) IIa (one chain) 50-100 25,000 (Ib-IX complexes) Vitronectin receptor von Willebrand factor receptor; binds thrombin Laminin receptor Fibronectin receptor Molecular Weight (unreduced) 142,000 95,000 138,000 9,600 Collagen receptor Receptors per Platelet Proposed Function 50,000 Fibrinogen and VWF receptor