Transfusions/Blood Products

pRBC

• Initial noninferiority RCT study in 2007, TRIPICU 

  • • Conclusion:  In stable, critically ill children a hemoglobin threshold of 7 g per deciliter for red-cell transfusion can decrease transfusion requirements without increasing adverse outcomes. 

• In 2018, a consensus panel came together to create guidelines for pRBC transfusions in critically ill children given the current literature- TAXI Guidelines

  • • Summary of recommendations are below

• In our PICU, we typically transfuse 15 ml/kg pf pRBCs

  • • • 1 unit is ~250-350ml when ordering for larger kids/adolescents.

      • If severely anemic (~ Hb < 5), transfuse small aliquots of ~ 5ml/kg over 4 hours to reduce risk for transfusion associated cardiac overload (TACO)

      • Chelated with citrate, and transfusion can cause hypocalcemia

• ~ 3 ml/kg of blood increases Hb by 1 point 

• Remember, hemoglobin (as delivered by pRBCs) increases your oxygen carrying capacity

  • • •  CaO2= Hgb(Sat)(1.34) + 0.003(PaO2) 

• Different preparations of pRBCs depending on patient's needs 

1. Leukoreduced -  filters out leukocytes and reduces the # of WBCs in the pRBC unit.

• Indications: HLA alloimmunization risk for potential organ transplant recipients, reduction of CMV transmission, reduced rated of febrile non hemolytic transfusion reactions, and peditric ECMO ~< 6mo (in case patient has SCID)

2. Irradiated- eliminates leukocytes in pRBC; irradiation decreases RBC viability and causes hyperkalemia, and thus irradiated just prior to transfusion in blood bank 

• Indications: HLA haplotype mismatch, immunocompromised, HSCT patients, neonates, congenital cell mediated immunodeficiencies

3. Washed - removes plasma proteins from pRBCs

• Indications: IgA deficiency, Red cell T activation, necrotizing enterocolitis, invasive pneumococcal infections, complement depended autoimmune hemolytic anemia, severe or recurrent allergic reactions with RBC transfusions

 Platelets

• Typically order 10mL/kg

• Stored at room temperature 

• Administer over 30mins -1h

• In 2022, TAXI-CAB guidelines were published to help guide transfusion decisions --> flowchart outlined below

Fresh Frozen Plasma (FFP)

• Contains multiple clotting factors, fibrinogen and coagulation proteins.

• The intrinsic INR of FFP is ~1.5, so giving it for an INR < or = 1.5 will not significantly benefit patient.

• Typically transfuse 15ml/kg

• In 2022, TAXI-CAB guidelines were published to help guide transfusion decisions --> flowchart outlined below

Cryoprecipitate

• Contains: Factor VIII, vWF, fibrinogen, Factor XIII --> higher concentration of fibrinogen than FFP so helpful to give if hypofibrinogenemic

• Ordered in units -->  Call blood bank to discuss amount to order

Oncologic Emergencies

Tumor Lysis Syndrome

• Occurs from rapid lysis of tumor cells. \

• Most commonly in ALL (WBC > 100,000) , AML (unstable cell membrane) and Burkitt Lymphoma

  • • • Can cause Hyperkalemia, hyperphosphatemia, hypocalcemia (from Ca binding Phos), hyperuricemia, all leading to AKI.

      • Can cause acute renal failure and need dialysis

• Treatment: Aggressive IVF hydration (do NOT put potassium in the fluids) ~ 2x mIVF, allopurinol or Rasburicase, possibly loop diureitcs, and if significant electrolyte abnormalities, dialysis 

Hyperleukocytosis/Leukostasis

• Typically defined as WBC >100k. Seen with AML/ALL.

  • • Much more common with AML - up to a  20-40% mortality

• Causes end organ damage by obstructing small arterioles/capillaries leading to strokes, intracranial hemorrhage, pulmonary edema, ARDS, myocardial infarctions, intestinal ischemia, renal failure, arterial and venous thromboses

• Treatment: 

  • • • Hyperhydration with crystalloid IV fluids (typically 2x maintanence) 

      • Cytoreduction with hydroxyurea/steroids with Heme/Once consultation

      • Rasburicase

      • Leukapheresis – the evidence based literature regarding this does not show a mortality benefit and is contraindicated in APML

      • Avoid blood product transfusion is possible 

Mediastinal Mass

• Can be seen in lymphoma, T-ALL,  or any leukemia with large lymph nodes

• Can present with signs and symptoms of SOB, orthopnea, poor exercise tolerance, bronchospasm, signs of decreased cardiac output (high HR)

  • • • Can also be asymptomatic

• ALL new onset oncologic purpses should get a simple CXR for this reason

• Management: Less is more with these patients!

  • • • NPO

      • IVF

      • Positioning as comfortable to patient

      • Support Respiratory status with non-invasive methods

        • • If respriatory distress, need multi-disciplinary team discussion for intubaiton including ENT, Anesthesia and ECMO circuit on standby (in case airway is lost and surgical bypass in required for patient survival)

      • NO SEDATIVES/NEUROMUSCULAR RELAXING AGENTS

      • Discuss with oncology about needs for diagnosis (biopsy vs flow cytometry) and then to start chemotherapy treatment 

        • • Some case require emergent chemotherapy/steroids to shrink mass and relieve symptoms

          • Can also consider emergen radiation

      • Needs CT scans chest/abdomen/pelvis if can lay flat

      • Needs Echocardiogram 

Coagulation / Anticoagulation

Anticoagulation

Factor X inhibitors:

• Unfractionated Heparin

  • Complexes with antithrombin III to inactivate clotting factors, most notably factor X

  • Often neonates and critically ill children will have relative antithrombin definciencies, in which case, escalating heparin doses will not improve therapeutic anticoagulation (can give antithrombin concentrate or FFP)

  • Used as continuous infusion for therapeutic anticoagulation and often SQ for prophylaxis (in adults)

• Low molecular weight heparin (enoxaparin (Lovanox), dalteparin (fragmin), tinzaparin, nadroparin)

  • Longer half-life than heparin, does not need to be given as continuous infusion

  • Does not require AT-III to function

  • Directly inhibits Xa

• Direct factor Xa inhibitors

  • Rivaroxaban (Xarelto), apixaban (eliquis), edoxaban (Lixiana), betrixaban (Bevyxxa)

  • Inhibits cleavage of prothrombin to thrombin by binding to factor Xa

  • These are all able to be taken PO

Vitamin K dependent antagonists (VKA)

• Warfarin

  • Inhibits vitamin K epoxide reductase (VKOR) which depletes vitamin K stores and prevents synthesis of factors 2, 7, 9, 10, protein C and S

  • Takes a few days to take effect because prevents new production but does not block circulating factors

  • Narrow therapeutic window - requires frequent monitoring, typically with INR

  • Taken PO

  • Kale, brussel sprouts and spinach (among other foods) have high levels of vitamin K and will decrease effectiveness (recommend eating a diet with consistent vitamin K intake)

  • Grapefruit juice enhances the anticoagulant effect (CYP enzyme inducer)

Direct Thrombin Inhibitors

• Bivalirudin (Bivalitroban)

  • Continuous infusion

  • Directly binds and inhibits thrombin

  • Often used for extracorporeal support (ECMO, cardiopulmonary bypass)

  • Indicated for patients with HIT

• Argatroban

  • Synthetic compound based on the structure of L-arginine. Binds reversibly to the active site of thrombin and inhibits its effect

• Dabigatran

Antiplatelet drugs

* these work by causing inhibition of platelet aggregation 

• Acetylsalicylic acid (Aspirin / ASA)

  • Irreversible inhibition of COX-1 activity in the prostaglandin synthesis pathway

  • Blocks production of thromboxane A2 which induces platelet aggregation (and vasoconstriction)

  • Takes a few days to take full effect, since platelets already in circulation already have TXA2 available. Only works to prevent production for new platelets. 

• Oral Thienopyridines (Clopidogrel (Plavix), Prasugrel (Effient), Ticagrelor (Brilinta),Ticlopidine, Cangrelor)

  • Selective inhibition of ADP-induced pletelet aggregation

  • These drugs inhibit platelet P2Y12 receptor

  • Ticagrelor causes bone marrow toxicity and is not used anymore

  • Prasugrel is most potent, fastest onset

  • Cangrelor is given IV

• Glycoprotein platelet inhibitors (Abciximab, Eptifibatide, Tirofiban)

  • Inhibit glycoprotein IIb/IIIa receptors on platelets

  • Decrease platelet aggregation

  • Only in IV form

• Protease-activated receptor-1 antagonists

• Vorapaxar

Antifibrinolytics 

• Aminocaproic acid (Amicar) and Tranexamic acid (TXA)

  • Prevent fibrinolysis, therefore help stabilize a clot from breaking down

  • Used in patients who are bleeding despite correction of coagulation factors

  • Often used in trauma patients, patients with chemotherapy induced mucositis, etc

  • Can be given IV continuously, in scheduled doses or topically

  • Lysine analogs, they competitively bind to lysine-binding sites on plasminogen, preventing it from binding to fibrin 

Thromboelastography (TEG)

• Functional whole blood test of the entirety of the coagulation system. 

• Provides much more information about why a patient might be bleeding or clotting, hypercoagulable or coagulopathic states

• Provides information regarding which factors might be defective or deficient and require replacement for the individual patients

• Often used in traumas, critical illness, post cardiopulmonary bypass, on ECMO