ABSTRACT
Neonatal alloimmune thrombocytopenic purpura
(lack the offending antigen and antibody)
PLASMA COMPONENTS
Fresh frozen plasma (FFP)
factor activity, 200-250 mL volume ●● WBCs non-functional (no cryoprotectant) ●● Leukoreduction and irradiation are
unnecessary ●● It is frozen within 8 hours and preserves
labile factors V and VIII
Uses of FFP
●● Invasive procedure planned in a patient with documented coagulation factor deficiency
replacement fluid for TTP, HUS
Contraindications for FFP
●● Do not give for volume expansion/nutritional support
●● Colloids or protein containing solutions better for volume expansion/nutritional support, as no risk of viral transmission
Cryosupernatant
●● Cryo poor plasma used in patients who are refractory to initial treatment with FFP
●● Lacks large molecular weight Von Willebrand multimers
●● Prepared by removing cryoprecipitate from FFP
Cryoprecipitate
●● Prepared by thawing 1 unit of FFP at 1-6°C and removing the supernatant
●● Contains fibrinogen, factor VIII C, factor VIII VWF, factor XIII
●● Small volume (10-15 mL) allows more rapid replacement of coagulation factors than a single unit of FFP (200 mL)
hemophilia, despite high levels of factor VIII
●● Recombinant or virus-inactivated products remain the first-line therapy for hemophilia
●● Not the “product of choice” for treating Von Willebrand disease
●● Pharmacologic agents (DDAVP) or virusinactivated concentrates (Humate P) are primary therapies for VW disease
HEMOLYTIC DISEASE OF THE NEWBORN (HDN)
jaundice
●● Hydrops fetalis (most severe HDN, often fatal in utero, extra-medullary hematopoiesis in the liver)
Abo HDN
size, and thus cannot cross the placenta ●● Group O moms, Group A or B babies ●● No intervention necessary unless very
severe
Rh HDN
cross the placenta ●● Not manifested in first pregnancy (unless
mother has prior history of transfusion) ●● D-ve moms, D+ve babies ●● Prevention: RhIG-commercially prepared
anti-D (RhoGam)
Lab testing
elevated ●● Increased change in amniotic fluid optical
density at 450 nm (Liley graph)
RhoGam
●● Prevents D antigen recognition in vulnerable moms
●● Obstetric indications → D-ve female at 28 weeks’ gestation, D-ve female within 72 hours of D+ve infant’s birth, D-ve female with pregnancy complications or invasive procedures (e.g., amniocentesis)
●● Dosage: One full dose vial (30 µgm) per 30 mL of D+ve whole blood
●● Kleihauer-Betke test-quantitative test (acid-resistant HbF; fetal RBCs stain brightly)
●● KB% × 5/3 = number of vials required to be injected
EXCHANGE TRANSFUSION
●● Exchange transfusion indicated for HDN, hyperleukocytosis, or sickle cell anemia
●● Purpose of exchange transfusion will determine recommended hematocrit and amount of fresh frozen plasma to be used in reconstituted unit
●● Compatability testing: Mother’s serum may be used for crossmatch
CONGENITAL HEMOGLOBINOPATHIES
Thalassemia
●● Transfusion improves oxygen-carrying capacity of blood
●● To suppress endogenous erythropoiesis that causes bony abnormalities
●● Transfuse every 3-4 weeks at a dose to maintain pre-transfusion Hb of 9.5-10.5 g/ dL and posttransfusion Hb of 13-13.5 g/dL
ABO SELECTION OF BLOOD COMPONENTS
When transfusing whole blood/packed RBCs
When transfusing plasma
SELECTION OF RBCs (IMMUNOLOGICAL CONSIDERATIONS)
●● Everyone can receive “O” RBCs. Most receive group-specific RBCs
●● D-positive individuals can receive D-positive or D-negative RBCs
NEONATES
blood group and maternal blood group ●● For simplicity, many transfusion services
transfuse group O to all neonates ●● Antibody screen must be done prior to
neonatal transfusion either using neonate’s serum or mother’s serum
●● Coagulation system is divided into five components: Vascular endothelium, circulating platelets, coagulation factors, coagulation inhibitors, and fibrinolysis
Vascular endothelium
tion by secreting platelet inhibitors such as prostacyclin PGI2 and nitric oxide, thus preventing platelet adhesion
●❑ It also secretes fibrinolytic proteins such as tissue plasminogen activator tPA and plasminogen activator inhibitor PAI
bogenesis; platelet adhesion stimulated by subendothelial collagen and von Willebrand factor (vWF)
●❑ Tissue factor activates the extrinsic coagulation cascade
●❑ Factors V and VIII are released triggering thrombosis
Platelets
●● Help in thrombosis by platelet adhesion (GP Ib), activation, and aggregation (IIb/IIIa)
●● Platelets cross-link to each other thus stabilizing the fibrin clot
Coagulation proteins
●● Extrinsic (factor VII and tissue factor), intrinsic (contact activation, XII, XI, IX, and VIII),
and the common pathway (X, V, prothrombin, thrombin, fibrinogen, fibrin, stable clot)
●● End result is cleavage of fibrinogen and formation of fibrin clot
●● Thrombin is the gatekeeper of the entire clotting cascade
Coagulation inhibitors
●● Antithrombin III and heparin cofactor II (both members of SERPIN family) inhibit the fact or Xa/thrombin pathway
●● Activated protein C/S prevent thrombogenesis by blocking factor Va and factor VIIIa in the clotting cascade
●● Tissue factor pathway inhibition is done by two serine protease inhibitors TFPI-1 and TFPI-2
Fibrinolysis
●● Process by which a thrombus/clot is removed from intravascular/extravascular site
●● The proteolytic enzyme that aides in this process is plasmin (produced from plasminogen)
HEMORRHAGIC DISEASE OF THE NEWBORN
●● Coagulation factors II, VII, IX, and X are produced in the liver and are dependent on vitamin K
●● After birth, the levels of these factors normally fall very rapidly
●● Unless vitamin K (1 mg intramuscularly) is administered prophylactically to all newborns, there may be risk of hemorrhage
●● Risk factors for vitamin K deficiency are antibiotic treatment, exclusive breastfeeding, conjugated hyperbilirubinemia
THROMBOPHILIA IN NEONATES AND CHILDREN
●● Genetic factors: Factor V Leiden, prothrombin mutation, protein S and C deficiency, antithrombin deficiency
●● Common sites of thrombosis in neonates: Renal veins, vena cava, central lines, catheter sites
should include AT III levels, protein C activity, free and total protein S antigen/activity, factor V Leiden, prothrombin G20210A, MTHFR T677T, fasting homocysteine level
●● If the mother has a history of lupus; perform circulating lupus anticoagulant and anticardiolipin antibodies
MATERNAL THROMBOPHILIA AND EFFECTS ON PREGNANT MOTHER/FETUS
●● Pregnancy is normally a thrombophilic state due to various factors (overall risk of venous thromboembolism in pregnancy is 1:1000)
●● An underlying genetic thrombophilia further enhances the prothrombotic features of pregnancy
●● The high thrombotic risk is caused by antithrombin III (AT III) deficiency, homozygous factor V Leiden, and the combined defect (factor V Leiden + prothrombin G20210A)
●● Uteroplacental circulation is compromised causing fetal growth retardation, fetal death, placental abruption, pre-eclampsia
●● Placenta shows multiple infarcts and fibrinoid necrosis of fetal vessels
INHERITED FACTOR DEFICIENCIES
recessive trait, disease manifested if factor VIII levels between 5% and 50%
●❑ Markedly prolonged aPTT, normal PT, and normal BT
●❑ Reduced factor VIII:C and normal vWF:Ag and ristocetin cofactor
●● Factor IX deficiency (hemophilia B, Christmas disease) ●❑ Clinically indistinguishable from hemo-
philia A ●● Von Willebrand disease
●❑ vWF is a large multimeric glycoprotein synthesized in megakaryocytes and vascular endothelial cells, stored in
Weibel-Palade bodies in endothelial cells and alpha granules of platelets
reduced vWF Ag, decreased ristocetin cofactor, decreased vWF multimers
cord separation, bleeding from umbilical stump, and hemorrhage at circumcision site
●❑ Screening test: Abnormal clot solubility in 5M urea
●● Antithrombin, protein C, and protein S deficiencies
replaced by glutamine ●❑ Bimodal peaks: Neonates and children
11-18 years old ●● Prothrombin gene 20210A mutation
●❑ Glutamine to arginine mutation at prothrombin gene at position 20210A
DISSEMINATED INTRAVASCULAR COAGULOPATHY (DIC)
●● Life-threatening microvascular thrombotic condition caused by a variety of insults
●● Laboratory screening: Prolonged aPTT, PT, elevated D-dimer and decreased fibrinogen, plasma factors, and platelets
THROMBOTIC MICROANGIOPATHIES
Thrombotic thrombocytopenic purpura (TTP)
●● Combination of profound thrombocytopenia, hemolytic anemia, and schistocytosis
●● Presence or absence of fever, neurologic symptoms, and renal failure
●● Primary and acquired TTP is caused by deficiency of ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor. May also be secondarily caused by drugs, infectious colitis
●● Platelet-rich thrombi noted in heart, pancreas, kidney, adrenal gland, brain, and other organs
●● Fibrin/red cell rich thrombi seen mostly confined to kidney
Stec-HUS
ing Escherichia coli (STEC-HUS) ●● E. coli O157:H7 accounts for 60% of cases
Atypical HUS
alternative complement pathway
Note
●● TTP and HUS are pathologically distinct entities, although they are clinically indistinguishable sometimes
●● Differentiation of TTP from HUS in pediatrics is critical
●● A life-saving treatment (plasma exchange therapy) is available for TTP, but only supportive therapy/renal dialysis for HUS