Thrombocytopenia in cancer and platelet transfusions

Thrombocytopenia is quite common in cancer patients; the main reasons for its development are presented in the table.

Causes of thrombocytopenia

Mechanism of development	Specific reasons	Patient contingent
Insufficient platelet production	Cytostatic/cytotoxic effects	Patients receiving radiation or chemotherapy
	Displacement of normal hematopoiesis	Patients with leukemia (out of remission and treatment) or metastatic bone marrow lesions
Increased destruction	Autoantibodies	Patients with chronic lymphocytic leukemia
	Splenomegaly	-
Increased consumption	DIC syndrome, massive blood loss, massive transfusion syndrome, use of artificial blood vessel or cell saver	Severe infection shock of various etiologies, surgical interventions
Platelet dysfunction	Linked to pathological protein, internal defect	Acute myeloid leukemia, myeloma disease, Waldenstrom's macroglobulinemia

The main danger of thrombocytopenia is the risk of developing hemorrhages in vital organs (brain, etc.) and severe uncontrolled bleeding. Transfusions of donor platelets allow preventing (prophylactic transfusions) or controlling (therapeutic transfusions) hemorrhagic syndrome in patients with thrombocytopenia caused by insufficient formation or increased consumption of platelets. With increased destruction of platelets, replacement transfusions are usually ineffective, although a hemostatic effect can be achieved with a significant increase in the dose of transfused platelets.

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Therapeutic transfusions

Specific indications for transfusion of donor platelets are determined by the attending physician depending on the clinical picture, causes of thrombocytopenia, the degree of its severity and the localization of bleeding, but there are a number of guidelines that must be remembered.

• The level of platelets in the blood >50x10 ⁹ /l is usually sufficient for hemostasis even during abdominal surgical interventions (bleeding time within the normal range is 2-8 min) and does not require transfusions. The presence of hemorrhagic syndrome in such patients is associated with other causes (impaired platelet function, vascular damage, DIC syndrome, overdose of anticoagulants, etc.).
• With a decrease in the platelet level (to 20x10 ⁹ /l or less), manifestations of hemorrhagic syndrome (hemorrhages and petechiae on the skin and mucous membranes, appearing spontaneously or with minor contact, spontaneous bleeding of the oral mucosa, nosebleeds) are most likely associated with thrombocytopenia. In spontaneous hemorrhagic syndrome against the background of thrombocytopenia <20x10 ⁹ /l, a transfusion of donor platelets is necessary. With a platelet level of 20-50x10 ⁹ /l, the decision is made depending on the clinical situation (risk of profuse bleeding, additional risk factors for bleeding or hemorrhage, etc.).
• Small-point hemorrhages on the upper half of the body, hemorrhages in the conjunctiva, fundus (precursors of hemorrhage in the brain) or clinically significant local bleeding (uterine, gastrointestinal, renal) oblige the doctor to perform an emergency platelet transfusion.
• Transfusion of platelet concentrate in case of increased destruction of platelets of immune genesis (antiplatelet antibodies) is not indicated, since the antibodies circulating in the recipient quickly lyse donor platelets. However, in case of severe hemorrhagic complications in a number of patients with alloimmunization, it is possible to achieve a hemostatic effect by transfusing large volumes of platelets from donors matched by HLA.

Prophylactic transfusions

Prophylactic transfusion of donor platelets to patients who do not have signs of hemorrhagic syndrome is indicated for:

• decrease in platelet levels <10x10 ⁹ /l (in any case),
• a decrease in platelet levels <20-30x10 ⁹ /l and the presence of infection or fever,
• DIC syndrome,
• planned invasive manipulations (vascular catheterization, intubation, lumbar puncture, etc.),
• a decrease in the platelet level <50x10 ⁹ /l during or immediately before abdominal surgery.

In general, the prophylactic use of platelet concentrate transfusions requires even more stringent consideration than the therapeutic use of replacement transfusions of donor platelets with minimal bleeding.

Transfusion technique and evaluation of effectiveness

Therapeutic dose is a dose that is highly likely to stop hemorrhagic syndrome or prevent its development, 0.5-0.7x10 ¹¹ donor platelets per 10 kg of body weight or 2-2.5x10 ¹¹ /m ² of body surface (3-5x10 ¹¹ platelets per adult patient). This amount of platelets is contained in 6-10 doses of platelet concentrate (multi-donor platelet concentrate, thromboplasm, platelet suspension) obtained by centrifuging one dose of donor blood. An alternative is TC obtained in a blood cell separator from one donor. One dose of such concentrate usually contains at least 3x10 ¹¹ platelets. Clinical efficacy depends on the number of administered platelets, and not on the method of their extraction, but the use of multi-donor platelet concentrate increases the number of donors with whom the patient "comes into contact". To prevent transfusion reactions and alloimmunization, the use of leukocyte filters is recommended.

The clinical criteria for the effectiveness of therapeutic transfusion of donor platelets are cessation of spontaneous bleeding and the absence of fresh hemorrhages on the skin and visible mucous membranes, even if the calculated and expected increase in the number of platelets in circulation does not occur.

Laboratory signs of the effectiveness of replacement therapy include an increase in the number of circulating platelets; after 24 hours, with a positive result, their number should exceed the critical level of 20x10 ⁹ /l or be higher than the initial pre-transfusion number. In some clinical situations (splenomegaly, DIC syndrome, alloimmunization, etc.), the need for the number of platelets increases.

The donor-recipient pair for platelet concentrate transfusion must be compatible in terms of ABO antigens and Rh factor, however, in everyday clinical practice it is permissible to transfuse platelets of the 0(1) group to recipients of other blood groups. It is important to follow the rules for storing platelets (store at room temperature), since at lower temperatures they aggregate, reducing the effectiveness of transfusions.