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H50 Hematology Toronto Notes 2023

Table 35. Characteristics of Select Non-Hodgkin Lymphomas

Follicular Lymphoma DLBCL Burkitt Lymphoma Mantle Cell Lymphoma

Percentageof NHLs 22-30% 33% <1% adult NHLs

30% childhood NHLs

c-Myc activation

6%

Genetic Mutation Bd -2 activation Bd -2, Bd - G, Myc

rearrangements

Aggressive|highgrade|

Previous CLl (Richter's

translormation: 5% CIL

patients progress to

DL8CL)

Overeipressionofcydin

01 (Bd-1activation )

Indolent

Male|M:F-4:1)

Classification

Risk Factors

Very aggressive

1. Endemic:African

origin. EBV associated

2. Sporadic:no EBV

3. HIV- related: AIDS

defining illness

Widespread painless LAD* Rapidly progressive LAD Endemic form:massive

and extranodal infiltration jaw LAD

Frequent transformationto 50% present atstage I/ll. "Starry-sky" histology

aggressive lymphoma

Very responsive to

chemoradiation treatment

Indolent

Middle-age - elderly

Clinical Features Often presents asstage IV with

palpable LAD

Involvement of Gl tract

50% widely disseminated High-risk of tumour lysis (lymphomatosis polyposis),

syndrome upon treatment Waldeyer's Ring

5 yr survival 25%

B symptoms present in 14 of

patients

t BM involvement

Malignant Clonal Proliferations of Mature

B-Cells

Table 36. Characteristics of B-Cell Malignant Proliferation

CLL Lymphoplasmacytic Lymphoma Myeloma

Rouleaux formation on peripheral

blood smear,if not artifact,denotes

hyperglobulinemia (but not necessarily

monoctonality)

Cell Type

Protein

lymph Nodes

Hcpatosplcnomegaly

Bone Lesions

Hypercalcemia

Lymphocyte Plasmacyloid Plasma cell

IqM if present

Very common

Common

I q M IgG. A.light chain (rarefy M. D.or E )

Common

Common

Rare

Rare

Common

Common

Rare Rare

Rare Rare

Renal Failure Rare Rare Common

Immunoglobulin Complications Common Rare Rare

Chronic Lymphocytic Leukemia

Definition

• indolent disease characterized by clonal malignancy of mature B-cells

Epidemiology

• most common leukemia in Western world

• mainly older patients; median age 70 yr

M>F

Pathophysiology

accumulation of neoplastic lymphocytes in blood, BM, lymph nodes, and spleen

Clinical Features

25% asymptomatic (incidental finding)

5- 10% present with B-symptoms (SI of: unintentional weight loss >10% of body weight within

previous 6 mo, temperature >38°C, or night sweats for >2 wk without evidence of infection), extreme

fatigue

lymphadenopathy (50-90%), splenomegaly (25-55%), hepatomegaly (15-25%)

immune dysregulation: autoimmune hemolytic anemia (DAT positive), I I P, hypogammaglobulinemia

± neutropenia

BM failure: late, secondary to marrow involvement by CLL cells r“i

L J

nvestigations

CBC: clonal population of B lymphocytes >5 x lO'Vl.

peripheral blood film

• lymphocytes are small and mature

• smudge cells

flow cytometry characteristics of peripheral blood

CD5, CD20dim, CD23, light chain restriction

cytogenetics: FISH (dictates response to therapy and prognosis) imaging must be done post-therapy to

ensure post treatment remission

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H51 Hematology Toronto Notes 2023

•B\1 aspirate

infiltration of marrow by lymphocytes in 4 patterns: nodular (10%), interstitial (30%), diffuse

(35%, worse prognosis), or mixed (25%)

Natural History and Treatment

•natural history:indolent and incurable;most casesshow slow progression

•small minority present with aggressive disease; usually associated with chromosomal abnormalities

(e.g. p53 deletion)

•first line therapy is dictated by cytogenetic status and patient co-morbidities

observation if early,stable, asymptomatic

treatment options vary by region;commonly fludarabine + cyclophosphamide + rituximab

(l-

'

CR) in fit patients age <65, with normal creatinine clearance and lack of 17p deletion/p53

disease

» chlorambucil (or venetoclax t obinutuzumab in the elderly)

ibrutinib or acalabrutinib in patients with unmutated IgVH and/or 17p deletion/p53

positivity

autoimmune phenomena:corticosteroids, rituximab

radiotherapy for isolated bulky nodes

•molecular therapies

idelalisib- PJ3K inhibitor

ibrutinib, acalabrutinib - BTK (Bruton’s tyrosine kinase) inhibitor

• venetoclax - Bcl

-2 inhibitor

Smudge cells are artifacts of damaged

lymphocytesfrom slide preparation

Prognosis

•9 yr median survival, but varies greatly

•prognosis: Kai staging, Binet staging or Revised CLL International Prognostic Index (includes age >65,

Rai/Binet stage, B2M, KiHV mutation status, I 7p del or TP53 mutation positivity)

Complications

•BM failure

•immune complications:AIHA,1TP, immune deficiency (hypogammaglobulinemia, and impaired

T-cell function)

•polyclonal or monoclonal gammopathy (often IgM)

•hyperuricemia with treatment

•5% undergo Richter’s transformation:aggressive transformation to diffuse large B-cell lymphoma (see

Table 35, H50 )

Multiple Myeloma g

Definition

• neoplastic clonal proliferation of plasma cells producing a monoclonal immunoglobulin resulting in

end organ dysfunction

• usually a single clone of plasma cells, although biclonal myeloma also occurs;rarely non-secretory

• preceded by smoldering myeloma or MGUS

Epidemiology

• incidence 3 in 100000, most common plasma cell malignancy

• increased frequency with age;median age of diagnosis is 68 yr;M>1

;

Pathophysiology

• malignant plasma cells secrete monoclonal Ab

95% produce M protein (monoclonal lg = identical heavy chain + identical light chain, or light

chains only)

IgG 50%, IgA 20%, IgU 2%, IgM 0.5%

15-20% produce free light chains or light chains alone found in either:

- serum has an increase in the quantity of either kappa or lambda light chain (with an

abnormal kappadambda ratio)

- urine has Bence-Jones protein

<5% are non-secretors

Clinical Features and Complications

• bone disease: pain (usually back), bony tenderness, pathologic fractures

• lytic lesions are classical (skull,spine, proximal long bones, ribs)

• increased bone resorption secondary to osteoclast activating factorssuch as P

'

l

'HrP

• anemia: weakness,fatigue, pallor

secondary’to BM suppression

• weight loss

• infections

usually S. pneumoniae and Gram-negatives

secondary to suppression of normal plasma cell function

• hypercalcemia: N/V, confusion, constipation, polyuria, and polydipsia

secondary to increased bone turnover

Multiple

<§>

Myeloma

SUM CRAB

Sixty percent plasma cells In BM

specimen

Light chain ratio >100

MRI lytic lesion >0.5cm

Calcium >2.80 mmol/L

Renal failure (Cr >176 mmol/L)

Anemia

Bony lesions(lytic lesions or

osteoporosisfelt to be caused by

myeloma)

Amyloid

. The general term for a variety of

proteinaceous materialsthat have a

similar structural organization and

are abnormally deposited in tissues

> Found in a variety of clinical

disorders and can cause systemic

(e.g. MM (light chains)) or localized

amyloidosis(e.g. Alzheimer disease

(AB amyloid))

L J

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H52 Hematology Toronto Notes 2023

•renal disease/renal failure

most frequently causes cast nephropathy (see Nephrology. NP35)

•bleeding

secondary to thrombocytopenia, may see petcchiac, purpura

can also be caused by acquired VWD

•extramedullary plasmacytoma

soft tissue mass composed of monoclonal plasma cells, purplish colour

•hyperviscosity: may manifest as headaches,stroke, angina, and Ml

rare in MM assecondary to increased viscosity caused by lgM protein (more common in WM/

LPL)

•amyloidosis

accumulation of insoluble fibrillar protein (lg light chain) in tissues; can cause infiltration of any

organ system:cardiac infiltration - diastolic dysfunction, cardiac arrhythmias,syncope,sudden

death; G1 involvement-malabsorption, beefy large or laterally scalloped tongue; neurologic

involvement- orthostatic hypotension, carpal tunnelsyndrome

may cause factor X deficiency if fibrils bind factor X -> bleeding (raccoon eyes)

•neurologic disease: muscle weakness, pain, and paresthesias

• radiculopathy caused by vertebral fracture and extramedullary plasmacytoma

• spinal cord compression (10-20% of patients) is a medical emergency

Investigations

•CBC Routine urinalysis will not detect light

chains as dipstick detects albumin.Need

sulfosalicytic acid or 24 h urine protein

(or immunofixation or electrophoresis

normocytic anemia,thrombocytopenia,and leukopenia

rouleaux formation on peripheral film

•biochemistry

increased Ca1 , increased tSR, decreased anion gap, increased Cr, albumin,[12-microglnbulin,

and LDH (as part of staging), and proteinuria (24 h urine collection)

•monoclonal proteins

SPEP:demonstrates monoclonal protein spike in serum in 80% (i.e.M protein)

UPEP:demonstrateslight chainsin urine = Bence-Jones protein (15% secrete only light chains)

immunofixation:demonstrates M protein and identifies lg type; also identifieslight chains

serum free light chain quantification:kappa and lambda light chains, calculated ratio

•BM aspirate and biopsy

» often focal abnormality, greater than 10% plasma cells, abnormal morphology, clonal plasma

cells;send for fluorescence in situ hybridization (F1SH) or cytogenetics (prognostic implications)

•skeletal series (x-rays), MR1 ifsymptoms of cord compression, PET imaging to pick up lytic lesionsin

asymptomatic MM

presence of lytic lesions and areas at risk of pathologic fracture

bone scans are not useful since they detect osteoblast activity

•elevated p2-microglobulin and LDH, and low albumin, are poor prognosticators

HBV surface and core Abs, and HBV surface antigen

Light Chain Disease

• 15% of MM produce only light chains

• Renal failure is a major problem

• Kappa > lambda light chain has

better prognosis

Serum Free Light Chain Ratiois an Independent

Risk Factor for Progression in MGUS

Hoad 2005:106:812-817

Purpose fodetermine whether the presence ol

monoclonal free kappa or lambda immunoglobulin

light chains« MGUS incieasesthe ink of progression

to malignancy.

Methods:Retrospective study with median folow up

of 15 yr.6aset re serum samples obtained from1383

MGUS patientsseen at the Mayo dime between 1960-

1884.1148 baselhe samples were obtained within

38 defd igossi

Results: Malignant piogiession had occjned m 8?

(7.6%) patients. In 379 (33%) patients, an abnormal

serum life l gM chain|FIC) ratio was delected.

There was a sign rficantly highernsJcof progression

in patientswith an abnormal FLC ratio relative to

patients with a normal ratio (hazard ratio.3.5:96%

Cl 2.3-5.S;P'

0.001).Thisfinding wasindependent

of the size and typeof the sera m nonodonal (M)

proton.In high- risk MGUS pa bents(abnormal seium

FIC ratio, non IgGMGUS. high seium M protein level

|>1.5 gm/dlD. the risk of piogiession at 20 yr was 58%

compared to 37% in high-intermediate-risk MGUS

(two irsk factors).21% low- intermediate risk (with

one risk factor)and 5% low-risk (no risk factors).

Condusinos:The presence ol an abnormal FLC ratio

is a clinically aod statistically significant predictor ol

progression n MGUS.Ibe low-risk subset of patents

with MGUS accoimtslor 40% of Ml MGUS patients and

hart a small lifetime risk ol progression, thusless

fotlow- up can be justified.

Diagnosis

•International Myeloma Working Group Criteria (“SLiM CRAB”):

• >60% clonal plasma cells on BM examination

light chain ratio (free,involved/uninvolved) of SlOO in the blood (involved must be at least 100

mg/L)

• MRI with more than one hone lesion (£5 mm)

CRAB - presence of end-organ damage related to plasma cell dyscrasia,such as:

increased serum Ca -1

'

renal failure

anemia

lytic bone lesions

Treatment

•non-curative

•treatment goals

improvement in quality of life (improve anemia, reverse renal failure, prevent fractures)

prevention of progression and complications

increase overallsurvival

•autologoustransplant if £70 yr

usually preceded by 4-6 mo of cytoreductive therapy:steroid based with novel agents(i.e.IMIDs

or Pis)

•transplant ineligible if >70 yr or comorbidities

pending on patient comorbidities can include a combination of: melphalan, prednisone,

cyclophosphamide, PI (i.e. bortezomib),IMIDs (revlimid),anti-CD38 agents (e.g. daratumumab)

•supportive management

bisphosphonates for those with osteopenia or lytic bone lesions (requires renal dosing)

local XRT for bone pain,spinal cord compression

kyphoplasty for vertebral fractures to improve pain relief and regain height

treat complications: hydration for hypercalcemia and renal failure, bisphosphonates for severe

hypercalcemia, prophylactic antibiotics, EPO for anemia, and DVT prophylaxis

•all patients will relapse; choice of retreatment regimen depends on duration of remission, organ

involvement, patient’s comorbidities, and preferences

LJ

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Prognosis

• International Staging System (ISS) (

f>2-microglobulin and albumin) used to stage and estimate

prognosis

• revised ISS for risk stratification:combination of original ISS, cytogenetic profile (i.e. p53 mutation

associated with poor survival and resistance to chemotherapy),and LDH

• median survival based on stage, usually 5-10 yr

Monoclonal Gammopathy of Unknown Significance

Definition

• presence of M protein in serum in absence of any clinical or laboratory evidence of a plasma cell

dyscrasia or lymphoproliferative disorders

incidence: 0.15% in general population, 5% of people >70 yr

asymptomatic

Diagnosis

• presence of a serum monoclonal protein (M protein) at a concentration <30 g/L

• <10% plasma cells in BM

• absence of SUM CRAB

• 03-1% of patients develop a hematologic malignancy each yr

» patients with M protein peak 15 g/L, abnormal free light chain ratio, or patients with IgA or IgM

MGUS are at higher risk of malignant transformation

patients with abnormalserum free light chains ratio are at increased risk of malignant

transformation

• monitor with history q6-12 mo, physical, CBC, Cr, calcium,albumin, LDH, and SPEP (considered

pre-malignant)

Lymphoplasmacytic Lymphoma

Definition

• LPL/VValdenstrom s macroglobulinemia

• proliferation oflymphoplasmacytoid cells

presence of monoclonal IgM paraprotein

Clinical Features

• chronic disorder of elderly patients; median age 64 yr

• symptoms:weakness,fatigue, bleeding (oronasal),weight loss,recurrent infections,dyspnea,CHE

(triad of anemia,hyperviscosity, plasma volume expansion), neurological symptoms, peripheral

neuropathy, and cerebral dysfunction

• signs: pallor,splenomegaly, hepatomegaly, lymphadenopathy, and retinal lesions

• key complication to avoid: hyperviscosity syndrome

• because IgM (unlike IgG) are large and confined mainly to intravascular space

Investigations and Diagnosis

• BM shows plasmacytoid lymphocytes

• bone lesions usually not present

• blood work rarely shows hypercalcemia

• cold hemagglutinin disease possible:Raynaud’

s phenomenon, hemolytic anemia precipitated by cold

weather

• normocytic anemia, rouleaux,and high ESR if hyperviscosity not present

• HBV, HCV serologies (note:can be associated with HCV; HCV eradication can put LPL into remission)

Treatment

• chemotherapy + rituximab (most commonly bendamustine + rituximab)

• if HCV positive -treat HCV prior to a trial of chemotherapy

• corticosteroids

• plasmapheresis for hyperviscosity:acute reduction in serum IgM

Waldenstrom'

s macroglobulinemia

accountsfor 8S% of all cases of

hyperviscosity syndrome

Complications of Hematologic Malignancies

Hyperviscosity Syndrome

Definition

• refers to clinical sequelae of increased blood viscosity (when relative serum viscosity >5-6 units),

resulting from increased circulating serum Igs or from increased cellular blood componentsin

hyperproliferative disorders(e.g.multiple myeloma,leukemia, PV )

• Waldenstrom’s macroglobulinemia accountsfor 85% of cases

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H54 Hematology Toronto Notes 2023

Clinical Features

• hypervolemia causing:CH!

:

, headache, lethargy, dilutional anemia

• CNS symptoms due to decreased cerebral blood flow: headache, vertigo, ataxia, and stroke

• retina shows venous engorgement and hemorrhages

• bleeding diathesis

due to impaired platelet function,absorption of soluble coagulation factors(e.g.nasal bleeding,

oozing gums)

• ESR usually very low

Treatment

• plasmapheresis,chemotherapy

Tumour Lysis Syndrome

Definition

• group of metabolic complications that result from spontaneous or treatment-related breakdown of

cancer cells

• more common in diseases with large tumour burden and high proliferative rate (high grade

lymphoma, acute leukemia)

Clinical Features

• metabolic abnormalities

cellslyse, releasing K •. uric acid, FO+s-flncreased levels)

PO-i

‘ binds Ca -(decreased Ca -’

)

• complications

lethal cardiac arrhythmia (increased K •)

acute kidney injury (formerly known as renal failure) see Nephrology, NP20

Treatment

• prevention

aggressive IV hydration

alkalinization not recommended due to risk of calcium phosphate or xanthine precipitation in

renal tubules

allopurinol (prevents uric acid accumulation) or rasburicase (lowers existing uric acid)

correction of pre-existing metabolic abnormalities

• dialysis

Blood Products and Transfusions

Blood Products

•RBCs, platelets, and coagulation factors (FP, cryoprecipitate, factor concentrates) are available for

transfusion

•donated blood (I U = 450-500 mL) is fractionated into these various components

centrifugation separates whole blood into RBCs and plasma

plasma isfurther fractionated

need to pool multiple units of platelets and WBCs to obtain therapeutic amounts

FP (previously known as FFP) is plasma frozen within 24 h of collection

cryoprecipitate isthe high MW precipitate generated when FP isthawed at low temperatures

single donor platelets and plasma can also be obtained by apheresis donations

Specialized Products

•irradiated blood products

prevent proliferation of donorT-cellsin recipients at risk of GVHD

used for patients with severe T-cell immunodeficiency, on purine analogue chemotherapy,with

Hodgkin lymphoma,candidatesfor BM transplant,or receiving directed transfusionsfrom firstdegree relatives, HLA-matched products,or intrauterine transfusions

•CMV-negative blood products

seronegative pregnant women

intrauterine transfusions

Blood Groups

Group Antigen Antibody

(on RBC) (in serum)

0 H Anti-A, anti-B

A A Anti-B

B B Anti-A

AB AandB Nil

In Canada, blood products are

leukodepleted via filtration immediately

after donation;therefore it is considered:

• Low in lymphokines, resulting

in a lower incidence of febrile

nonhemolytic transfusion reactions

• CMV safe (because CMV isfound in

leukocytes)

n

Red Blood Cells L.J

®

Packed Red Blood Cells

• stored at 4'

C

• shelf life is 42 d after collection

• infuse each unit over 2 h (max of 4 h)

1 unit of pRBC will increase Hb by +

approximately10 g/L

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H55 Hematology Toronto Notes 2023

Indications for Packed RBC Transfusion

• Hb <70 g/L;this may change as per patient’s tolerance orsymptoms

maintain Hb between 70 and 90 g/L during active bleeds

• consider maintaining a higher Hb for patients with:

• CAD/unstable coronary syndromes

• uncontrolled, unpredictable bleeding

Selection of Red Cells for Transfusion

• when anticipating an RBC transfusion,the following should be ordered:

• group and screen: determines the blood group and Rh status of the recipient as well asthe

presence of auto- or alloantibodies against major/minor blood group antigens in the patient’s

plasma

cross-match:involves mixing the recipient’s blood with potential donor blood and looking for

agglutination (takes 30-45 min)

• when blood is required,several options are available

• lst-line:fully crossmatched blood, electronic crossmatch is becoming more widely used ( not

always available in emergency situations)

• 2nd-line: donor blood of the same group and Rh status as the recipient

• 3rd-line:O- blood for females of reproductive age:0 'blood for all others

American Society of Hematology

Choosing Wisely Recommendation

Do not transfuse more than the minimum

number of RBC units necessary to

relieve symptoms of anemia or to return

the patient to a safe Hb range (70-80

g/L) in stable non-cardiac patients

Platelets

Table 37. Platelet Products

Product Indication

Random Donor (Pooled)

Single DonorPlatelets

HIA MatchedPlatelets

Thrombocytopenia with bleeding

Potential BMIrecipients.Refractory to pooled platelets

Refractory to pooled or single donor platelets,presence of HLA Abs

See Landmark Hematology Trials

for more information on the FOCUS

trial.It details theefficacy of liberal

or restrictive transfusion in high-risk

patients after hip surgery • stored at 20-24°C

• random donor platelets come in a pool of 4 units; while a unit of apheresis platelets comes from a

single donor

• 1 platelet pool should increase the platelet count by >fox 10’/L

• if an increase in the platelet count is notseen post-transfusion: autoantibodies(i.e.I I P),

alloantibodies (Anti-HLA or Anti-HPA),consumption (bleeding, sepsis, DIG),or hypersplenism may

be present

Table 38. Indications for Platelet Transfusion

Pit (x lO’

l/ ) Indications

«10 Non-immune thrombocytopenia

Procedures not associated withsignificant bloodloss

Procedures associated withblood lossot major surgery (>500 mt estimated blood loss)

Pre-neurosurgery or head trauma

Platelet dysfunction (or antiplatelet agents) and marked bleeding

<20

«50

«100

Any

Relative Contraindications of Platelet Transfusion

• TTP, HIT, post-transfusion purpura, and HELLP

Coagulation Factors

Table 39. Coagulation Factor Products

Product Indication

FP Oepletion of malt p

'

e coagulation factors (e.g. sepsis. OIC. dilution.TTP HUS.Inrer disease),emergency

reversal of life-threatening bleeding secondary to warfarin overdose when factor concentrates are not

available

Hemophilia A (Factor VIII deficiency) and von Willebrand disease - use in emergencies when specific factoi

concentrates arenot available

Hypofibrinogenemia

Hypofibrinogenemia

von Willebranddisease and Hemophilia A

factoi VIII deficiency (Hemophilia A)

Factor IX deficiency (Hemophilia B)

Facloi VII deficiency withbleedmgi'surgery.Hemophilia A oi B with inhibitors,tlanrmann's thrombasthenia

Reversal of warfarin therapy or vitamin K deficiency in bleeding patient or inpatient requinng uigent («6 h)

surgical procedure,urgentnon-specific “reversal" of direct Xa inhibitors

Group & Screen vs.Cross-Matching:

G&S:ABO group+Rh factor

Cross-Matching:match recipient's serum

with donor's packed RBC or Abs

Cryopreciprtate (enriched

fibrinogen.VWF.VIII.XIII)

Fibrinogen Concentrate (FC)

HumatePorWilate

Factor VIIIconcentrate r1

L J

Factor IXconcentrate

Recombinant factor Vila

Prothrombin complex concentrate:

PCC

(0ctaplex .Beriplex:

) +

Activated prothrombin complex

concentrate:aPCC (FEIBA)

Hemophilia A or B with inhibitors

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H56 Hematology Toronto Notes 2023

Acute Blood Transfusion Reactions

DDx of Post

-Transfusion Fever

• Acute hemolytic transfusion reaction

• Febrile non hemolytic transfusion

reaction (FNHTR)

• Bacterial contamination

• Allergy

IMMUNE

Acute Hemolytic Transfusion Reactions

• ABO incompatibility resulting in intravascular hemolysissecondary to complement activation, occurs

immediately alter transfusion

• most commonly due to incorrect patient identification

• risk per unit of blood is <1/40000

- presentation:fever, chills, hypotension, back or flank pain, dyspnea, hemoglobinuria

• acute renalfailure (<24 h) and DIC

• treatment

stop transfusion

notify'blood bank and check for clerical error

send new specimen to blood bank for repeat testing and draw hemolysislabs:CBC, bilirubin,

LDH, reticulocytes, DAT

• maintain BP with vigorous IV fluids ± inotropes

• maintain urine output with diuretics,crystalloids, dopamine

Febrile Nonhemolytic Transfusion Reactions

• due to alloantibodies to VVBC, platelets or other donor plasma antigens,and release of cytokinesfrom

blood product cells

• occurs within 6 h of transfusion

• risk per unit of blood is 1/100 (minor), 1/10000 to 40000 (severe)

• presents with fever ± rigors,facial flushing,headache, myalgia

• look forserioussymptoms of shaking, chills/rigors, hypotension, tachycardia,anxiety, dyspnea, back/

chest pain, N/V

• treatment

rule out hemolytic reaction or infection

• if temperature <39°C and no serioussymptoms, continue with transfusion but decrease rate and

give antipyretics

if temperature >39°C or presence ofserioussymptoms,stop transfusion,investigate the reaction,

and startsupportive measures

Allergic Nonhemolytic Transfusion Reactions

• alloantibodies(IgH) to proteinsin donor plasma result in mast cell activation and release of histamine

• occurs mainly in those with history of multiple transfusions or multiparous women

• risk per unit of blood is 1/100

• presents mainly as urticaria and occasionally with fever

• can present as anaphylactoid reaction with bronchospasm, laryngeal edema, and hypotension

(1/40000)

• can occur in some IgA deficient patients with anti-IgA

• treatment

mild:slow transfusion rate and give diphenhydramine

moderate to severe:stop transfusion,give IV diphenydramine,steroids,epinephrine, IV fluids,

and bronchodilators

DDx of Post

-Transfusion Dyspnea

• Transfusion-associated circulatory

overload (TACO)

• Transfusion-related acute lung injury

(TRAL1)

• Allergy (bronchospasm/anaphylaxis)

Transfusion-Related Acute Lung Injury

• new-onset acute lung injury that occurs during transfusion or within 6 h of transfusion completion

profound hypoxemia (PaO’

/FiOT <300 mmHg)

bilateral pulmonary edema on imaging

no clinical evidence of left atrial hypertension or if present, judged not to be the main contributor

• pathogenesis uncertain; perhaps due to binding of donor Abs to WBCof recipient and release of

mediators that increase capillary permeability in the lungs

• typically occurs 2-4 h post-transfusion and resolves in 24-72 h

• risk per unit of blood is 1/10000

• is currently the leading cause of transfusion-related morbidity and mortality

• treatment:supportive therapy (oxygen)

• inform blood bank; patient and donor testing will be arranged

NONIMMUNE

Transfusion-Associated Circulatory Overload

• due to impaired cardiac function and/or excessively rapid transfusion

• presentation:dyspnea, orthopnea, hypertension, tachycardia, crackles at base of lungs, and increased

venous pressure

• incidence: 1/100

• risk factors: age >70 yr, heart failure,history of Ml, renal failure, positive fluid balance

• treatment:stop transfusion, give diuretics, and oxygen.Transfuse at lower rate ± diuretics to prevent

+