5. Article
• Journal: The New England Journal of Medicine
• Published : July 11, 2019
• Authors: Sandhya R. Panch, M.D., M.P.H., Celina Montemayor-Garcia,
M.D., Ph.D., and Harvey G. Klein, M.D.
6. INTRODUCTION
• 15℅ of inpatients receive blood transfusion
• 1 ℅ of them suffer severe adverse effects
• 5℅ – Hemolytic transfusion reaction
• Bystander Hemolysis
7. HISTORY
• Mid 17 th Century – First documented reaction
• Landsteiner’s discovery of ABO blood groups in 1900
• Ottenberg- Routine pretransfusion testing
• Development of anticoagulant–preservative
• Combination of serologic techniques and molecular identification of
the corresponding red-cell genes (compatibility testing)
8. Epidemiologic Features
• Hemolysis was the most common cause of transfusion-associated
death during the 1976–1985
• Least common fatal complications (1/1,972,000) red-cell units
transfused in 2016
• “Wrong blood in the tube”
• Delayed hemolytic reaction- 1 in 500 to 1 in 1000
9.
10. PATHOPHYSIOLOGY
• Acute hemolytic reactions:
• Pre-existing IgM, and less commonly IgG
• Complement Activation (C5 through C9)
• Hemolysis
• Increased free Hgb
• ATN
11.
12.
13. Pathophysiology
• Delayed hemolytic reaction:
• Incomplete complement activation (C3a and C5a)
• Proinflammatory cytokines
• Bradykinin and Kallikrein system activation
• Vasodilation, Hypotension DIC
14. • severe hemolytic reactions
• long-term transfusions
• part by the release of cell-free hemoglobin,
• activates leukocyte-driven
• inflammasome pathways and causes endothelial
• dysfunction through nitric oxide scavenging
• post-transfusion haemoglobin levels falling below the pretransfusion values
Pathophysiology
15. • Passenger lymphocyte syndrome
• solid-organ transplantation
• Incompatibility between the donor’s plasma and the recipient’s red cells,
“minor ABO incompatibility”
• viable donor B lymphocytes, termed “passenger lymphocytes,”
• develop 5 to 14 days after heart– lung, liver, kidney, intestinal
transplantations, as well as after hematopoietic stem-cell infusions
Pathophysiology
16.
17. CLINICAL
Suspected AHTR
Signs & Symptom: Fever,chills,rigor, flank pain reddish urine
,hypotension, dyspnea, sense of “impending doom,”
oliguria, anuria, bleeding Timing: minutes to hours after
transfusion
Stop transfusion immediately,
repeat clerical check
• Ancillary tests: positive DAT, hemoglobinemia,
hemoglobinuria, low haptoglobin, high LDH, elevated direct
or indirect bilirubin, high D-dimers, increased fibrinogen, PT
or PTT (if DIC is present), BUN, or creatinine
Repeat and confirm ABO,
Rh, antibody compatibility;
repeat DAT
Immune-mediated hemolysis:
aggressive hydration Severe cases:
pressor support, renal consultation,
management of coagulopathies
Perform Gram's stain and blood
cultures to rule out acute
Infections Rule out drug-induced
hemolysis, nonimmune causes
18. CLINICAL
Suspected DHTR
Signs and symptoms: fatigue, pallor, jaundice
Timing: 2 days to 1 month after transfusion
or infusion
Obtain detailed patient history: record of
multiple or recenttransfusions, including IVIG,
platelets, plasma; HSCT; history of
alloimmunization, pregnancies, or
transplantation
Ancillary tests: new positive antibody screen, incompatible
cross-match, decreased hemoglobin, positive DAT or IAT, low
haptoglobin, high LDH, elevated indirect bilirubin, spherocytes
or microspherocytes on peripheral smear, reticulocytosis
Management: cautious transfusion with antigen-negative,
cross-match– compatible units In severe cases: immune
modulators (glucocorticoids, IVIG, rituximab, erythropoietin-
stimulating agents)
19.
20. Management
• Supportive care
• Prompt interruption of the transfusion
• Saving of the remaining blood in the unit for testing
• Blood and Urine sampling
• ICU along with a renal consultation (dialysis)
21. • Vigorous hydration with isotonic saline
• Maintain urine output at a rate above 0.5 to 1 ml/kg/hr
• ? Mannitol
• Supplemental diuretics
• Sodium bicarbonate (130 mmol per liter in 5% dextrose) at a starting
at 200 ml /hr to achieve a urinary pH >6.5
• Hyperkalemia
• Vasopressor : dopamine infusion (2 - 10 μg /kg/min)
Management
22. • In DIC (bleeding, platelets, FFP and cryoprecipitate)
• platelet >20,000 per cubic ml
• INR < 2.0
• fibrinogen > 100 mg/Dl
• No evidence supports the routine use of therapeutic high-dose
glucocorticoids, intravenous immune globulin, or plasma exchange
Management
23. • Transfusion of incompatible units
• prophylaxis with glucocorticoids (hydrocortisone at a dose of 100 mg,
administered just before transfusion and repeated 24 hours later)
• IV IG (1.2 to 2.0 g /kg, administered over a period of 2 to 3 days, with the first
dose given just before the incompatible transfusion)
Management
25. • Preventing passenger lymphocyte syndrome
• A recipient with blood group A receiving a transplant from a group O donor
should receive group O red cells and group AB plasma
• Prophylactic plasma reduction in the donor graft, partial red-cell exchange
Management
27. • Patients who are already heavily alloimmunized and require long-
term transfusion support, Prophylactic
• Rituximab (1 to 2 gm iv)
• Inj methylprednisolone
• Patients with sickle cell disease
• glucocorticoids
• intravenous immune globulin
• rituximab
• erythropoiesis-stimulating agents
Prevention
28. SUMMARY
• HTR are important cause of transfusion-associated reactions and may
be subclinical, mild, or lethal
• Electronic verification systems
• Other reactions
• Delayed hemolytic transfusion reactions,
• Hyperhemolysis
• Passenger lymphocyte syndrome in transplant recipients
• Preventive strategies
• Systematic protocols
