Heparin Induced Thrombocytopenia in Recurrent Acute Thromboflebitis in Chronic Myeloid Leukaemia.
Authors: Corinaldesi Giorgio , Corinaldesi Christian 
Published: April 2020

Abstract
The CML is characterised by t(9:22) (q34;q11) and is associated with the expression of the BCR/ABL complex which plays an important role in the evolution of the CML by coding an oncoprotein p-210 TK, with a clinical proceeding that can be divided into three phases: chronic, accelerated, and blastic, where other cytogenetic modifications occur (trisomy 8, inv 16, iso 17q, t(15:17), t(8:10), t(15:19), associated with a reduced therapeutical response, refractoriness, and associated with the onset of other symptoms, such as fever, night sweats, bleeding, bone pain, abdominal discomfort, weight loss, focal swelling, increase of the number of abnormal blasts.
The iatrogenic effects of haematological toxicity with significant cytopenias are often observed during the therapeutical scheme of the CML, (pegINF-alfa2b + imatinib, alfa IFN + ARA-C), or in the management of refractory or relapsed disease or drugs resistance (usually geldanamycin, homoharringtonine, arsenic trioxide, farnesyl-transferase inhibitor, ubenimex, actinonin, or bortezomib). We have identified 7 patients (6 men and 1 female) with CML, all patients had a complete hematologic response (CHR), but with a different molecular and cytogenetic response, for this reason every patient received a second cycle of therapy in order to consolidate the chronic phase; this therapeutical scheme consisted on imatinib (STI571) 400 mg/daily + pegINF-alfa2b 100 mg/weekly.
All patients developed DVD (5 lower limb DVD, 2 upper-limb DVD) as a consequence of CML, and they were all treated with heparin: UFH (5 patients, loading dose of 5000 U followed by continuous infusion of at least 35000 U/24h) or LMVH: nadroparine (2 patients 5700 U/daily), and have presented HIT (heparin induced thrombocytopenia) 4–7 days after initiation of heparin, nadir &lt;30% below 50000 platelet fall from baseline. This disorder depends on IgG class antibodies-mediated platelet activation and subsequent cross-linking of platelet Fc-gammaR-IIa thus forming PF4/heparin/IgGcomplexes; 2 cases had no clinical manifestations and ELISA seropositivity confirmed the diagnosis, while 5 cases presented ASR (acute systemic reaction): erytematous skin lesions or haematoma, bleeding gums, epistaxis, haematuria. In these patients the traditional treatment consists of discontinuing heparin therapy followed by administration of alternative anticoagulant, the biggest risk factors in the development of bleeding complication is the timing and the choice of the agent, dosing criteria, peak drug concentration, interaction with other therapy. Patients with LMC have an increased risk of major bleeding and the magnitude of the risk can be stratified according to the presence or absence of clinical risk factors: myelodepression, chemotherapy, dismegakaryocytopoiesis, or it may also have an autoimmune origin due to haemotransfusions and the development of antiplatelet antibodies against the GPIIb/IIIa, or GP1b/V/IX; this shows the importance of the in vivo stimulation of MP (megakaryocite progenitors) with TPO + IL-1, IL-6, SCF, IL-11. In order to prevent the possible immune dysregulation it may be used metylprednisone and cyclosporin. We have treated patients with HIT with fondaparinux 2.5 mg, and they did not have any bleeding event or recurrent VTE after 11 months of follow-up with a good quality of life. Although this study examined only a small set of patients these findings suggest the convenience of an anticoagulation treatment in the management of selected cases.