Clinical Use of Blood Components

สมใจ กาญจนาพงศ์กุล

James Blundell (27 December 1790 Holborn, London – 15 January 1878 St George Hanover Square, London) was

an English obstetrician who performed the first successful transfusion of human blood to a patient for treatment of a haemorrhage.

Blood Components

• Red cell concentrate

• Plasma

• Platelet concentrate

• Cryoprecipitate, prepared from fresh frozen plasma; rich in Factor VIII and fibrinogen

• Cryoprecipitate removed plasma

Indications for blood transfusion

• To increase the oxygen capacity of blood by giving red cells. • To restore the blood volume to maintain effective tissue perfusion. • To replace platelets, coagulation factors and other plasma proteins.

Blood may be needed in the following circumstances: Blood loss: - Bleeding - Trauma Inadequate production: - BMF - chronic blood diseases - thalassemia - leukemia Excessive destruction of cells: - Diseases - Mechanicals Transfusion of blood and products should be undertaken only to treat a condition that would lead to significant morbidly or mortality that cannot be prevented or managed effectively by other means.

Dosage Blood

components Dosage and

Administration Increment

RBC ABO compatible

Adult : 2-3 unit Ped : 10-15 ml/kg *(2 x Hb X BW)

Transfusion rate 3‐5 mL/kg/hr Should be completed in 4 hrs

1 unit- Hb 1g/dL Hb 2-3 g/dL

FFP ABO compatible

10-15 ml/kg

CRP 10-15 ml/kg Factor IX 7-10%

CPP (Cryo) 0.2 unit/kg Fibrinogen 80-100 mg/dL

Platelet concentrate

Adult : 4-6 PC / 1SDP Ped : 0.2 unit/kg 10 ml/kg in preterm NB Transfusion rate 1‐2 mL/min

20,000-40,000 / cu.mm.

Duration times for transfusion

When to transfuse?

Hemoglobin Level and Symptoms

HGB (g/dL) SYMPTOMS

9-11 MINIMAL

7.5 EXERTIONAL DYSPNEA

6.0 WEAKNESS

3.0 DYSPNEA AT REST

2-2.5 HEART FAILURE

LINMAN NEJM 279:812, 1968

Red blood cell transfusion guidelines

• Each of the guidelines recommended

strictive transfusion strategy with most advising a Hb threshold of 7 g/dL in asymptomatic patients.

• American Society of Anesthesiology task force guidelines recommended a restrictive hemoglobin transfusion strategy between 6-10 g/dL

(determined by the potential for ongoing bleeding and other clinical variables)

In symptomatic patients, these guidelines suggest that transfusion should be administered to prevent symptoms.

• The European Society of Cardiology recommended transfusion for patients with a hemoglobin level of less than 7 g/dL unless the patient is not hemodynamically stable.

• The American College of Physicians recommended a hemoglobin transfusion threshold of 7-8g/dL in hospitalized patients who have either coronary heart disease or acute coronary syndrome.

• The British Committee for Standards in Haematology recommended hemoglobin level be maintained at 8 -9 g/dL.

• The National Comprehensive Cancer Network recommended a hemoglobin transfusion goal of greater than 10 g/dL.

Red blood cell transfusion guidelines

RBC Transfusion Recommendations* for Hospitalized, Hemodynamically Stable Patients in Specific Clinical Situations

*Table adapted from: Red Blood Cell Transfusion: A clinical practice guideline from the

AABB. Ann Intern Med 2012;157:49-58 and Clinical practice guidelines from the AABB: Red blood cell transfusion thresholds and storage. JAMA. doi:10.1001/jama.2016.9185.

How should hemorrhagic shock be treated?

• Some patients with mild blood loss can be managed with crystalloid, but patients with severe (class III and IV) hemorrhage will require blood replacement therapy.

Dehmer JJ, Adamson WT: Massive transfusion and blood product use in the pediatric trauma patient.

Semin Pediatr Surg 2010;19(4):286-291.

Spinella PC, Holcomb JB: Resuscitation and transfusion principles for traumatic hemorrhagic shock.

Blood Rev 2009;23(6):231-240.

Classes of hemorrhage Class I hemorrhage: The patient has lost up to 15% of his or her blood volume. Otherwise healthy patients are likely to have minimal tachycardia and no other symptoms. Unless there is ongoing hemorrhage, the patient should require no treatment.

Class II hemorrhage: The patient has lost 15% to 30% of his or her blood volume. Loss of this amount of blood stimulates the compensatory mechanisms usually associated with early, compensated shock. Tachycardia, increased respiratory rate, and narrowed pulse pressure are seen. Urine output is usually maintained, but the patient may have signs of early central nervous system impairment. Such signs may include fright or anxiety.

Class III hemorrhage: The patient has lost 30% to 40% of his or her blood volume. This amount of blood loss is clearly associated with signs of compensated shock but may also be associated with uncompensated shock. Even healthy individuals may have a drop in systolic blood pressure with this degree of blood loss. Urine output is likely to be decreased, and the patient may be very anxious or confused.

Class IV hemorrhage: This represents loss of more than 40% of the circulating blood volume. This degree of hemorrhage is uniformly fatal if untreated. The shock state may, in some cases, be irreversible. The patient has a markedly decreased blood pressure. He or she can be expected to have complete peripheral vasoconstriction, extreme tachycardia, and little or no urinary output. Mental status is very depressed, and the patient may be unconscious.

Blood Volume Loss Of:

• 15 - 30 percent -- should be treated with crystalloids or colloids, not RBCs, in young, healthy patients;

• 30 - 40 percent -- requires rapid volume replacement, and RBC transfusion is probably necessary;

• >40 percent -- is life-threatening and volume replacement, including RBC transfusion, is required

Emergency Release of Blood Products

An emergency release of blood products is warranted when the clinical setting precludes waiting for completion of pretransfusion and compatibility testing. • Severe, ongoing life-threatening hemorrhage • Life-threatening anemia

What you should do: • Notify blood bank of need for emergency release of RBCs • Complete hospital’s “emergency release” form • Send patient blood sample to blood bank ASAP (before emergency transfusion begins, if possible) What you’ll get from the blood bank (depending on how much testing has already been performed): • Uncrossmatched RBCs (ABO group-specific if determined on a current blood specimen) • Group O RBCs if blood bank has not documented patient’s ABO group on a fresh blood sample

Top‐up transfusion

• in order to raise Hb in symptomatic chronic anaemia, often due to blood sampling in sick NB infants.

Exchange transfusion

• The main indication for neonatal exchange transfusion is to prevent neurological complications (kernicterus) caused by a rapidly‐rising unconjugated bilirubin concentration.

Transfusion of Neonates and Infants

Recommendations for neonatal top-up transfusion (10-15 ml/kg)

Postnatal age Transfusion threshold HB (g/dL)

Ventilated On O2/CPAP Off O2

0-24 hours of life < 12 < 12 < 10

Day 1-7 < 12 < 10 < 10

Week 2 ( days 8-14 ) < 10 < 9.5 < 7.5 – 8.5

Week 3 ( > day 15 ) < 8.5

General Guidelines For Small-volume Transfusion To Infants

• Less controversial are the results from the TRIPICU (Transfusion Requirements in the Pediatric Intensive Care Unit) study, which demonstrated a hemoglobin threshold of 7 g/dL for red-cell blood transfusion is not inferior to a treatment strategy using a hemoglobin threshold of 9.5 g/dL among critically ill but stable children being treated in ICUs.

• A higher threshold may be indicated for patients with cardiovascular disease or children with severe hypoxemia, hemodynamic instability, active blood loss or cyanotic heart disease.

General Guidelines For Small-volume (10-15 mL/kg)Transfusion To Infants:

Case study 1 • ดช. ไทย อาย ุ5 ปี 10 เดือน refer จาก รพ.เอกชน เร่ืองซีด สงสยั

Thalassemia แต่หาเลือดให้ไม่ได้ ขณะนอนท่ี รพ เอกชนด้วยปัญหาเร่ืองไข้สงู ไอ หอบ 5 วนั BW 19.1 kg

• PH: คลอดครบก าหนด มีตวัเหลืองต้องส่องไฟ 2 วนั Blood group A; Rh + CBCD2 : Hct 22% WBC 15,950 plt. 1,038,000/cu.mm.

MCV 58.3 MCH 18.3 MCHC 31 RDW 20.9 Retic 1.79%, DCT neg, G6PD normal, Hb-typing -pending

การรักษา : cefotaxime, ventolin, O2

GM ขอ PRC แต่ไม่มี anti B ใน serum จงึส่งมา รพ เด็ก

Case study 1

Problems

• Pneumonia

• Anemia + ABO discrepancy

Case study 1

Anemia – Cause? Management? Need Transfusion? Cause of anemia? PBS- hypomicrocytic 2+, fragment few Feeding – นม 8 oz x 3 ขวด ข้าว 3 มือ้ ใส่ซีอิว้ขาว ไม่กนิผัก/เนือ้สัตว์ Serum ferritin 17

Case study 1:How to manage?

Anemia - Dx : Nutritional anemia

Treatment

fer-in sol 4 mkd

folic 1 tab OD

F/U 1 mo

Hct 33.9% MCV 61.2

น าผล Hb typing รพ เอกชน A2A

(A2 2.5)

Case study 1

ABO discrepancy

identify blood group กาชาด-ใช้เวลา

(ผล ABsubgroup, Rh pos )

in Urgency setting ควรเลือกใช้อะไร?

PRC – A, O

FFP - AB

Case study 1 : ABO Subgroup

ABO subgroup เป็นหมูเ่ลือดท่ีมี แอนติเจน A และ B ใน ปริมาณน้อยบนเมด็เลือดแดง

ดงันัน้ในการตรวจหมูเ่ลือดต้อง ตรวจด้วยวิธีหลอดทดลองและต้องตรวจทัง้ cell grouping และ serum grouping แปลผลร่วมกนัซึง่จะท าให้พบความไมส่อดคล้อง (ABO discrepancy) ต้องค้นหาสาเหตเุพื่อวินิจฉยัหมูเ่ลือดได้ถกูต้อง

แตถ้่าเป็นผู้ ป่วยที่จ าเป็นต้องรับโลหิตเร่งดว่นอาจให้ packed red cell หมู ่O Rh (D) เหมือนผู้ ป่วย (เพราะการวินิจฉยัหมูเ่ลือดต้องใช้เวลาในการพิสจูน์)

Current consensus guidelines for red cell transfusion

Summary : in the major patient categories

• Major haemorrhage - rapid transfusion based on clinical parameters,

• Slow onset "medical" anaemia : iron, vitamin B12 or folic acid deficiency

avoid transfusion and give the appropriate replacement therapy

• Anaemia following surgery - keep a comfortable margin above any critical point

Hb 7g/dI for younger, otherwise healthy patients

Hb 9g/dl for older (>60 yrs) patients / known heart disease

Acute blood loss: – 30% of volume of blood

• Patients in critical or intensive care - 7g/dl (9g/dl if cardiac disease)

• Transfusion dependent patients:

Thalassemia major - 10g/dl

Other indications - transfuse to optimise QoL measures, such as fatigue

Fresh frozen plasma • No clinical studies have been done to determine whether correcting

coagulation abnormalities (elevated prothrombin time [PT]/INR) with transfusion of fresh frozen plasma (FFP) affects outcomes in severe sepsis and septic shock.

• However, there are no studies that show that correction of coagulation abnormalities helps patients who are not bleeding, even if their INR is severely elevated. Given this absence of any demonstrated benefit.

• The Surviving Sepsis Guidelines suggest reserving transfusion of FFP for those patients with severe sepsis/septic shock who have increased PT, partial thromboplastin time, and/or INR, and who either have active bleeding, or are planned to undergo surgery or invasive procedures.

Blood transfusion practices in sepsis

28

Thrombocytopenic bleeding

• Risk of bleeding – platelet count

– cause of thrombocytopenia

– comorbid disease

– drugs

• Clinical manifestations – petechiae

– purpura, ecchymoses

– mucosal bleeding

– menorrhagia

– intracranial bleeding

Risk of thrombocytopenic

hemorrhage in AML

0

10

20

30

40

0 20 40 60 80 100

Platelet count (x 10^9/L)

% d

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Platelets • There is no solid evidence to guide platelet transfusion in severe

sepsis and septic shock, but a restrictive approach is suggested, unless bleeding or the risk thereof is present.

• For patients with severe sepsis and septic shock, the Surviving Sepsis Guidelines suggest transfusing platelets prophylactically only when platelets fall to 10,000/mm3, assuming no bleeding is present.

• In patients considered at significant risk for bleeding, a threshold of 20,000/mm3 is suggested.

• For those with active bleeding or who are undergoing surgery or invasive procedures, transfusing platelets to 50,000/mm3 is suggested.

• However, 100,000 /mm3recommended for brain surgery or high velocity injuries.

Blood transfusion practices in sepsis

Case study 2

• ดญ.ไทย อาย ุ2 เดือน ปรึกษาจาก PICU รับ refer จาก รพจ เร่ือง ซมึ เกร็ง ชกัมา 4 วนั มี status epilepticus มีประวตัิ maternal amphetamine user, on infant formular

CBC Hct 28% , WBC 1,810 (N21 L58 Mo6 band5%), Plt 16,000 AST 344/ ALT41 Albumin 2.57 Coagulogram INR 1.29, aPTT 40.9 (ratio 1.54) CT brain scattered hypodensity in both cerebral hemisphere , bilat lat. ventricle dilatation and tiny subdural hematoma Ddx : ischemic/ infarct/ infect/ trauma

Case study 2

• D2 of admission

PICU ปรึกษาเร่ือง thrombocytopenia จะต้องเข้า OR neuro Sx required plt > 100,000 แตห่า PC ให้ไมไ่ด้เน่ืองจาก มี poly-

agglutinable cell

Case study 2

How to manage? • Neuro Sx required plt > 100,000 • After 0.4 unit/kg of PC transfusion platelets = 104,000 • Go on to OR for operation

Transfusion issues in polyagglutination

• Transfusion protocols that have been advocated for T-activated patients include the use of washed or plasma- reduced red blood cells and platelets, and the use of low anti-T-titre plasma if fresh-frozen plasma is essential.

• A `slow' transfusion with close evaluation of possible hemolysis has also been recommended

Platelet refractoriness

• defined as a CCI less than 7500 for at least two sequential platelet transfusions

• Corrected Count Increment (CCI) for platelets: CCI = (platelet increment) x (BSA in m2)

number of platelets transfused (x 1011)

• The expected CCI (10-60 minutes after a platelet transfusion)

> 7,500 (representing 20-30% platelet recovery)

Platelet refractoriness

Platelet Products and Substitutes

Infusible Platelet Membranes (IPMs) • manufactured from outdated platelet units. • Platelet-derived microparticles (microvesicles) - particles that form

spontaneously from a platelet during collection and processing of components.

• have the ability to function as a platelet, procoagulant-active, adhere to the vascular subendothelium and enhance platelet adhesion to form a primary hemostatic plug.

• application for IPMs - in patients who are refractory to platelet transfusions and for whom finding human leukocytic antigen (HLA)-matched platelet pheresis donors is difficult. One problem appears to be a relatively short life (less than 24 h) in vivo.

FFP

Indications • bleeding patients with -multiple coagulation factor deficiencies secondary to liver disease -urgent reversal of warfarin therapy -disseminated intravascular coagulation (DIC) -dilutional coagulopathy resulting from massive blood or volume replacement -congenital factor deficiencies for which there is no coagulation concentrate available, such as deficiencies of Factor V, XI • plasmapheresis : thrombotic thrombocytopenic purpura

(TTP) and haemolytic uremic syndrome

Cryoprecipitate Indications

• contains factor VIII/vWF , fibrinogen, fibronectin, and factor XIII

• used for the correction of inherited /acquired coagulopathies

Recommendations

• bleeding patients with hypofibrinogenemia, von Willebrand's disease and patients with haemophilia A (when factor VIII concentrate is not available)

• Prophylaxis in non bleeding perioperative or peripartum patients with congenital fibrinogen deficiencies or von Willebrand's disease unresponsive to 1-desamino-8-D-arginine vasopressin (DDAVP).

• Correction of microvascular bleeding in massively transfused patients with fibrinogen concentrations less than 80–100 mg/dl

Cryoprecipitate Reduced Plasma

• Cryoprecipitate Reduced Plasma (CRP) is the plasma remaining once the cryoprecipitate has been prepared. Preparation of the cryoprecipitate removes much of the fibrinogen, Factor VIII and vWF from the plasma.

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