Transcript Hematology in the ICU - UBC Critical Care Medicine

Hematology in the ICU
Yoan Lamarche
• A 42 yo patient presents to the ER 3
weeks after allogenic hematopoietic
stem cell transplant for acute myeloid
leukemia. His principal complaint is
fever and cough.
1.
Classify hematologic malignancies
and outline the principles of
treatment. (Noemie)
Yoan
Lamarche
Principles of treatment
• Radiation
• Can be used alone in stage 1A Hodgkin Lymphoma
• In Combination therapy for initial bulky sites to tumor
burden
• Used for solitary plasmacytoma in MM
• Chemotherapy
• Induction Rx
• Complete Remission (eg. Normal CBC & <5% BM blast
in AML)
• Consolidation Rx
• Intrathecal chemo: eg. ALL
• Biologics:
• eg. interferon, Imatinib (BCR/ABL inhibitor for CML)
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Lamarche
Principles of treatment
• Bone Marrow Transplant
– Source of cells: bone marrow, peripheral blood or
umbilical cord blood
– Auto: Donor is also recipient
• No GVHD
• Allows higher doses of chemo
• Used for lymphoma and MM
– Allo: Immunologically distinct
•
•
•
•
Used for AML, ALL, CML, CLL, MDS, lymphoma
Used in nonmalignant diseases: eg.Aplastic anemia
Desired effect of Graft vs tumor BUT  risk of GVHD
Followed by immunosuppression to prevent rejection
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Lamarche
2.
What are the complications of hematopoietic
stem cell transplant leading to ICU admission
(Todd)
3. Explain the principles of treatment of
infectious and non infectious complications of
hematopoietic stem cell transplant. (Todd)
Yoan
Lamarche
Life-threatening complications of
HSCT
• Non-infectious
– Cardiogenic pulmonary edema
• From chemo conditioning (cyclophosphamide)
or chronic chemo (anthracycline)
• Pericarditis (+/- tamponade or arrhythmias)
from radiation
– Noncardiogenic pulmonary edema
• Diffuse Alveolar Damage (analogous to ARDS)
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Lamarche
Life-threatening complications of
HSCT, continued
• Diffuse Alveolar Hemorrhage
– Rarely with gross hemoptysis; usually progressive hypoxia,
dyspnea, tachycardia within 2 weeks of HSCT
– CXR --> patchy interstitial +/- airspace opacification, initially
involving mid-zones, spreading outward
– Dx is with bronchoscopy, where progressively bloodier returns are
noted with repeated BAL
– Pathophysiology: ??? Pre-transplant airway inflammation
– High mortality (up to 90%)
– Treatment: Pulse steroids (according to a retrospective study in
1994…)
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Lamarche
Life-threatening complications of
HSCT, continued
• Interstitial lung disease (usually associated
with aggressive chemo, including
cyclophosphamide, doxorubicin and cisplatin)
• Pneumonitis:
– Aspiration (ie mucositis and opiates)
– Idiopathic interstitial pneumonitis and ARDS or
fibrosis (high mortality)
• Non-pulmonary: Hepatic veno-occlusive
disease (may --> fulminant hepatic failure)
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Lamarche
Infectious complications
• Preengraftment as well as immediately and
late (> 3 mo) postengraftment
• Bacterial, fungal and viral pathogens lie in
wait at each stage.
• Immunosuppression (including neutropenia)
is the key factor
– Including chemo conditioning period
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Lamarche
The Usual Suspects
•
•
•
Bacterial:
– Aerobic gram positive and gram-negative organisms
• Psuedomonas (<1% of allogeneic SCT pts), legionella and
bacillus in particular
Fungal:
– Candida (mucocutaneous or invasive) and aspergillus are most
common
• Fusarium, zygoycetes, and others are increasingly recognized
Viral:
– CMV (pneumonia, enteritis, retinitis, encephalitis, marrow
suppression, FUO…)
– HSV (VZV late postengraftment)
– HHV 6, 7,8 (fever, pneumonitis, encephalitis)
– EBV (pneumonia)
– Adenovirus (pneumonitis, nephritis, hemorrrhagic colitis,
hemorrhagic cystitis)
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Lamarche
The Usual Suspects (don’t forget
Verbal Kint)
• Parasitic:
– PCP (or PJP), rare due to chemoprophylaxis
– Toxopasmosis
– Mycobacteria (TB, avum)
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DAHHemosiderin
laden
macrophages
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Prophylaxis
• Viral: Acyclovir through day 30 (HSV),
gancyclovir through day 100 (CMV)
• Bacterial: Quinolone during neutropenia
• Fungal: Fluconazole through day 75
(candida)
• Parasitic: TMP/SMX through day 180 or end
of immunosuppression (PCP)
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Lamarche
Quinolone x neutropenic phase
Fluconazole x 75d
Acyclovir 30d
TMP/SMX x 180d or end immmunosupp
Gancyclovir 100d vs PCR q week
On initial assessment, the patient is anxious and coughing,
his RR is 30 and HR 110, his BP is 95/40, he is 38ºC, O2
Sat is 88% on RA after administration of 2L NS by the
emergency team.
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Lamarche
The patient is admitted to the ICU for
observation, investigation and treatment
4. What should be the initial workup and choice
of Rx (Todd)
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Lamarche
Treatment
• Low threshold for broad spectrum coverage,
especially in critical care setting. Keep
presenting syndrome in mind, but be
prepared to jump on septic
immunosuppressed patients like a spider
monkey.
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Lamarche
For our patient
• Early postengraftment (i.e.
immunosuppressed), with pulmonary sepsis
syndrome (RR, Temp, HR).
– Prophylaxis, chemo and CBC/Diff unknown
• Initial broad coverage to include gram
positive/negative bacteria (including
psuedomonas
– Imipenem 500 mg IV Q 6 hrs
– Add antifungal or antiviral if no improvement by
day 5, or if clinical picture evolves to suggest
these pathogens
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Lamarche
For our patient, continued
• Investigations: Pan-culture (not CSF at this
point, but would have low threshold to LP if
LOC changes or neurological complaints
develop)
• Imaging: CXR initially
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Lamarche
Tube?
• Goal directed therapy as with any other septic
patient, with careful consideration of possible
cardiomyopathy in setting of chemo
• Decision to intubate would be similar to any
other septic patient; the poor outcome
associated with multiorgan failure in this
population would warrant consultation with
heme regarding his prognosis (nb recent pt in
SPH ICU)
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Lamarche
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Shorr, Pulmonary Infiltrates in the Non-HIV- Infected Immunocompromised Patient CHEST / 125/1/ JANUARY 2004
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Lamarche
The patient is now in your ICU. His Sat is better with O2,
his RR is now 25 and less labored. His CBC indicates
Hb of 82, Plt of 19 000 and WBC count of 2, Creat is
200 and LFTs indicate N AST/ALT, Total Bilirubin is
100, Direct bili is 12, GGT N, LDH 200 . The patient
has a urine output of 20 cc/hr for the first 2 hours, the
patient appears more confused and complains of
blurred vision.
5.
What are the possible diagnoses leading to this
constellation of symptoms (Noemie)
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Lamarche
Q#5 What are the possible diagnoses leading to this
constellation of symptoms?
• 42 yo 3 wks post ABMT for AML presents
with fever and cough
• Becomes more confused and complaining of
blurred vision
• T 38, RR 25, u/o 20 cc/hr in 2 hours
• Hb 82, Plt 19, WBC 2, Cr 200, AST/ALT N,
T.Bili 100, D.Bili 12, GGT N, LDH 200
Yoan
Lamarche
Q#5 What are the possible diagnoses leading to this
constellation of symptoms?
• 42 yo 3 wks post ABMT for AML presents
with fever and cough
• Becomes more confused and complaining of
blurred vision(?)
• T 38, RR 25, u/o 20 cc/hr in 2 hours
• Hb 82, Plt 19, WBC 2, Cr 200, AST/ALT N,
T.Bili 100, D.Bili 12, GGT N, LDH 200
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Lamarche
What are the possible diagnoses leading to this
constellation of symptoms?
• Fever in post BMT
– ?infection, ?drug fever, ?TTP, rejection?
• Renal failure
– ?Pre-renal, microvascular, toxins/meds, ATN
• Hemolysis
– Transfusion reaction (Combs?), TTP?, DIC?
• Acute blurry vision
– ?retinal detachment, neuritis, retinal vascular
occlusion, uveitis, acute glaucoma
• Cytopenia
– ?rejection, hemolysis, malignancy, DIC/sepsis
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Lamarche
What are the possible diagnoses leading to this
constellation of symptoms?
• DDX:
– TTP: classical pentad
– DIC  ? Coags, ? Fibrinogen
– Transfusion rxn  ? Combs, blurry vision
uncommon
– GVHD  no mucositis, ?hemolysis and blurry
vision uncommon
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6.
What are the risk factors associated with
development of TTP (Scot)
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5.
What is the physiopathology of TTP (Naisan)
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TTP blood smear
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5.
What are the diagnostic criteria for TTP
(Naisan)
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Lamarche
An update on the pathogenesis and management of acquired
thrombotic thrombocytopenic purpura
Helen Yarranton and Samuel J. Machin. Curr Opin Neurol 16:367–373.
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5.
Explain the treatment modalities for TTP,
what is the outcome after treatment, are
there reports of recurrence (Scot)
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Lamarche
• PLEX – infusion presumably supplies missing
ADAMTS-13 protease, and exchange
removes any acquired autoantibody and
unusually large VWF multimers.
– Schedule – initially daily until platelet count has
normalized and hemolysis has ceased.
– Recommended volume is one plasma volume.
• Adjunctive treatments – steroids,
immunosupressants (rituximab, cyclosporine)
may reduce production of autoantibodies in
poorly responsive, relapsing or resistant
disease.
• Prognosis - Relapses rate 36%, higher in those with
a severe deficiency of ADAMTS 13 activity; half of
such patients may have a relapse, most within a
year.
• Long-term follow-up data suggest a diminished
frequency of relapses over time, though a relapse
can occur years after the initial episode.
• Small case series have suggested lower rates of
relapse after splenectomy or the use of rituximab.
• Current recommended approach to pat ients in
remission is only to ensure prompt medical attention,
including a complete blood count , in the event of any
systemic symptoms that may suggest relapse.
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Lamarche
You manage the patient for two weeks in you
ICU, the patient eventually needed a short
intubation, no pressors, and no renal
replacement therapy. The patient is now
afebrile, his initial leucopenia has resolved
and his platelet count is 182 000. You agree
with the BMT team for a transfer on the
hematology ward.
10. What blood tests should be monitored
(Marios)
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Lamarche
INVESTIGATIONS FOLLOWING TREATMENT OF
HSCT RELATED THROMBOTIC MICROANGIOPATHY
The patient should have regular CBC checks with a repeat
hemolysis work-up should his platelets and hemoglobin drop.
This would include a total and direct bilirubin, LDH, haptoglobin,
and a peripheral blood smear.
Given this is most likely not idiopathic TTP, an ADAMTS13 level
would be of no benefit, as levels are typically normal or not
severely decreased in transplant-related thrombotic
microangiopathy.
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Lamarche
References
George JN. Thrombotic thrombocytopenic purpura. N Engl J Med
2006;354:1927-1935
Ho VT, Cutler C, Carter S, et al. Blood and Marrow Transplant Clinical Trials
Network toxicity committee consensus summary: thrombotic microangiopathy
after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant
2005;11:571-575.
George JN, Li X, McMinn JR, Terrell DR, Vesely SK, Selby GB. Thrombotic
thrombocytopenic purpura-hemolytic uremic syndrome following allogeneic HPC
transplantation: a diagnostic dilemma. Transfusion 2004;44:294-304.
Kojouri K, George JN. Thrombotic microangiopathy following allogeneic
hematopoietic stem cell transplantation. Curr. Opinion in Oncology
2007;19(2):148–154
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Lamarche
10. What are the long term outcomes of
patients after BMT requiring ICU treatment
(Neil)
Yoan
Lamarche
ICU outcomes in BMT
• Mortality rates vary (40-89%)
• No good pre admission predictors
• Highest mortality during ICU stay were
–
–
–
–
–
–
Hemodialysis
Mechanical ventilation
Pulmonary artery catheterization
Multiorgan failure
Advanced age
Airway/pulmonary invasion by tumor
• Authors emphasize that treatment is not futile
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Chest 2002
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On its way up from the 2nd to the 5th floor, the elevator has a malfunction
and falls 3 floors abruptly. The patient and his nurse are injured.
The double code blue is called as they open up the elevator on the 2nd
foor.
•
The nurse is unconscious, face down in a significant amount of blood.
Her breathing is labored and she is tachycardic at 140. Her sBP is 80.
You log roll her, her nose seems to be the source of the bleeding. You
intubate her after having an IV access and you administer 2 liters of
NS. The nose bleed remains serious. You administer 2 O- units of
PRBCs to the patient and send stat blood work. She rapidly regains
consciousness as your resuscitation progress. The ENT resident packs
her nose. You get the CBC and coags back: Hb 100, WBC 14, Plt 150
000, INR 1.2 and PTT 42.
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Lamarche
Your BMT patient was well braced in his
stretcher and has no external injuries. He is
intubated for hypotension. You transitorily
loose his pulse during intubation. 1 minute of
CPR and 3 L of NS later, the patient sBP is
back at 100. The patients drops again, you
administer 3 Units of PRBC and obtain a CXR
that is N, a FAST US is negative, but
suboptimal. A CT abdo reveals a significant
pelvis hematoma (20cm x 15 cm)
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Lamarche
12. Explain your initial approach to the
coagulopathic patient (Neil)
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Lamarche
Initial approach to Coagulopathic
Patient
• ABC’s
• Recussitation
– RBC’s
– FFP
• II, V, VII, IX, X, XI, AT III
– Platelets
– Cryoprecipitate
• vWF, VIII, Fibrinogen, fibronectin
– Factors (see Factor first card)
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Lamarche
Initial approach to Coagulopathic
Patient
•
•
History
– Nature of Bleeding
– Sites of Bleeding
– Patterns of Bleeding
– Medications
– Associated diseases
– Family History
Physical
– Vitals
– Skin
– Mucosa
– Lymphadenopathy
– Liver size
– Joints
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Lamarche
Initial approach to Coagulopathic
Patient
• Lab investigations
–
–
–
–
INR = extrinsic/common pathway
PTT = intrinsic/common pathway
Platelet count and bleeding time
Fibrinogen = hypoproduction or overconsumption
• Altered by preg, malignancy, sepsis
– Thrombin time = fibrinogen and inhibitors
– D-Dimer = Fibrin degradation products
– Factor Level assays
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Lamarche
12. Illustrate the coagulation cascade and the
fibrinolytic pathway (Neil)
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Fibrinolytic Pathway
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..\Transfusion Therapy\Use of rFVII in Trauma.pdf
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Lamarche
12. Identify the sites of action of
anticoagulants, platelet inhibitors,
fibrinolytics and antifibrinolytics (Noemie)
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Lamarche
Q#14 Identify the sites of action of anticoagulants,
platelet inhibitors, fibrinolytics and antifibrinolytics
• Heparin and LMWH
– Binds to
Antithrombin
– Conformational
change in AT
– Potentiates binding
capacity to thrombin
and Factor Xa
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Lamarche
Identify the sites of action of anticoagulants, platelet
inhibitors, fibrinolytics and antifibrinolytics
• Direct thrombin
inhibitor
– Lepirudin,
argatroban and
bivalirudin
– Do not require a
plasma cofactor like
heparin
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Lamarche
Identify the sites of action of anticoagulants, platelet
inhibitors, fibrinolytics and antifibrinolytics
• Warfarin
– Interferes with
synthesis of vitamin
K depentdant factors
– Factors II, VII, IX, X
– Prevents the
carboxylation
process which is
necessary to activate
the clotting factors
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Lamarche
Identify the sites of action of anticoagulants, platelet
inhibitors, fibrinolytics and antifibrinolytics
• Aspirin
– Inhibits thromboxane A2
synthesis
– activation and
recruitment to site
• Clopidogrel and Ticlopidine
– Block ADP receptor on
platelet surface
– Metabolized through
P450delayed onset
• GPIIb/IIIa antagonists
– Block binding of
fibrinogen to activated
GP IIb/IIIa
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Lamarche
Identify the sites of action of anticoagulants, platelet
inhibitors, fibrinolytics and antifibrinolytics
• Fibrinolytics
– Goal is rapid thrombus
dissolution
– All promote conversion of
plasminogen to plasmin
– Plasmin then degrades
the fibrin matrix of clot
– New generation:
alteplase, tenecteplase
and reteplase (activate
fibrin bound
plasminogen)
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Lamarche
Identify the sites of action of anticoagulants, platelet
inhibitors, fibrinolytics and antifibrinolytics
• E-Aminocaproic
Acid and
Tranexamic Acid
• Competitively block
binding of
plasminogen to
fibrin
• Tranexamic acid 10
times more potent
• 2-4 hour half life
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Lamarche
Summary
Warfarin
Fibrinolytics
Aspirin
Clopidogrel
IIb/IIIa inhibitors
AT
Heparin
Argatroban
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Fibrinolytic Pathway
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• The nurse continues to bleed. You notice in
her wallet a medic-alert card stating she has
von Willebrand’s disease.
15. What are the principles of management of
the bleeding von Willebrand disease patient
(Marios)
Yoan
Lamarche
Factors to consider before treating
1. Nature and severity of the type of VWD present
(type 3 doesn’t respond to DDAVP, type 1 almost always
does, and type 2 may or may not)
2. Location and severity of the bleeding episode or challenge
(different treatments will be given depending on severity)
3. Response to the treatment of prior bleeding episodes
(DDAVP should only be attempted in minor bleeds in pts
known to have responded in the past)
4. Other medications and illnesses impacting hemostasis
(Assess need for FFP, platelets, vitamin K, or protamine)
Yoan
Lamarche
Minor bleeding
In patients with type 1 or 2 VWD who previously showed a good
response to DDAVP:
Initial treatment should begin with DDAVP 0.3 mcg/kg (max. 20 mcg) IV
or 150-300 mcg intranasally every 12 h for 2-4 doses.
Response can be assessed both clinically and with the ristocetin
cofactor activity level which should reach at least 30 IU/dL, and
preferably 50 IU/dL
The antifibrinolytics agents aminocaproic acid and tranexamic acid
should be used as adjuvants (doses on next slide)
Yoan
Lamarche
Minor bleeding
If the patient continues to bleed, has not had a previous trial of
DDAVP, or is a known non-responder to DDAVP:
VWF concentrate should be given at 30-60 ristocetin cofactor
units per kg followed by 20-40 ristocetin cofactor units per kg q
12-48 hr to keep VWF level >30 IU/dL for 3-5 days.
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Lamarche
Major bleeding
1. Treatment should be initiated with VWF concentrate:
Initial dose of 40-60 ristocetin cofactor units/kg x 1
Then 20-40 ristocetin cofactor units/kg every 12-24 hr
Goal VWF level 50-100 IU/dL for 7-14 days.
2. Antifibrinolytics should be given in addition to the concentrate:
Tranexamic acid 50 mg/kg every 4 to 6 h OR
Amnocaproic acid 10 mg/kg every 8 hours
3. Recombinant factor VIIa can be considered in type 3 VWD
with serious refractory bleeding
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Lamarche
Acquired VWD
1. Trial of DDAVP; levels of VWF activity should be monitored for
possible rapid clearance
2. In patients who do not respond adequately to DDAVP, VWF
concentrates should be used. Patients with circulating inhibitor may
require very large doses of VWF (50 to 100 U/kg)
3. If the patient does not respond to DDAVP, and especially in
patients who have documented antibody-mediated acquired VWD, a
trial of high-dose IVIG (1g.kg per day for 2 days) can be attempted
4. Treatment of the underlying disease should be undertaken if
feasible
5. If all else fails, recombinant Factor VIIa can be tried
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NEJM351(7) 2004
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• The patient’s condition gets better with
significant blood component therapy. The
junior resident in your team asks about
alternatives to transfusions.
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16.
Even if you are busy resuscitating 2 patients, you
take 1 minute to outline the options (Naisan)
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Current Opinion in Anaesthesiology 2004, 17:139–143Blood substitutes
Fahim A. Habib and Stephen M. Cohn
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Hb based carriers
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Perfluorocarbons (PFCs)
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Perfluorocarbons (PFCs)
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Are they safe?
Natanson et al, JAMA, May 21,
2008—Vol 299, No. 19
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As your resuscitation evolves, you notice
progressive hypoxia in the patient.
17. What are the complications of blood
transfusion and their physiopathology?
(Marios)
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Lamarche
ACUTE COMPLICATIONS
Occur within minutes and up to 8 hours post-transfusion:
1. Acute hemolytic transfusion reaction
2. Febrile nonhemolytic transfusion reaction
3. Simple allergic transfusion reaction
4. Severe allergic or anaphylactic transfusion reaction
5. Transfusion-related circulatory overload (TACO)
6. Transfusion-related acute lung injury
7. Sepsis
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Lamarche
DELAYED COMPLICATIONS
Occur from 2 days to years post-transfusion
1. Delayed hemolytic transfusion reaction
2. Transfusion-associated graft-versus-host disease
3. Post-transfusion purpura
4. Transfusion-transmitted diseases
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Lamarche
ACUTE HEMOLYTIC TRANSFUSION
REACTION
Occurs within minutes or up to 4h post-transfusion
Incidence: 1:38 000
Mortality: 1:30
Etiology
1. ABO incompatibilty: usually due to a clerical error
2. Other blood group alloantibodies from prior pregnancy or
transfusion
3. Group O platelet transfusion with high anti-A or anti-B
titers to non-O patient (rare)
Clinical presentation
Fever and chills
Hemoglobinuria
Yoan
Less common: pain, hypotension, nausea/vomiting, dyspnea, renal
Lamarche
failure, DIC
FEBRILE NON-HEMOLYTIC
TRANSFUSION REACTION
Occurs during transfusion or up to 4-6h post-transfusion
Incidence
RBC 1:526
Platelets 1:10 per pool
Etiology
Circulating cytokines in the donor plasma
Recipient antibodies against donor leukocytes (less common since
implementation of universal leukoreduction in 1999)
Clinical presentation
Fever is most common
May be associated with chills, rigors, nausea, vomiting, and
hypotension
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Lamarche
SIMPLE ALLERGIC TRANSFUSION
REACTION
Occurs during transfusion or up to a few hours post-transfusion
Incidence: 1:3 to 1:300
Etiology
Recognition of antigens in donor plasma by preformed recipient IgE
antibodies.
Clinical presentation
Urticarial rash that resolves with antihistamine administration.
May also be associated pruritus, erythema, flushing, or mild airway
symptoms (cough, wheezing), nausea, vomiting, abdominal crams, and
diarrhea
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ANAPHYLACTIC TRANSFUSION
REACTION
Usually occurs within minutes but can occur up to 4h post transfusion.
Incidence 1:20 000 to 1:50 000
Mortality 3%
Etiology (vast majority are unexplained)
Transfusion of an allergen to a sensitized recipient
Passive transfer of IgE (to drugs, food) to the recipient
Anti-IgA in IgA-deficient patients
Antibodies to polymorphic forms of serum proteins (haptoglobin, IgG,
albumin, C3, C4, transferrin, alpha-1-antitrypsin)
Clinical presentation
Urticaria, stridor/wheezing, hypotension, nausea, vomiting
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TRANSFUSION-ASSOCIATED
CIRCULATORY OVERLOAD (TACO)
Occurs during transfusion or up to 6h post-transfusion
Incidence < 1:100 (higher in patients with CHF)
Etiology
Circulatory overload from impaired cardiac function and/or
excessively rapid rate of transfusion
Clinical presentation
Dyspnea, orthopnea, hypoxia, tachycardia, increased venous
pressure, increased PCWP, hypertension, elevated BNP
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Lamarche
TRANSFUSION-RELATED ACUTE
LUNG INJURY
Occurs during transfusion or up to 6h post-transfusion
Incidence 1:5000
Etiology (three major theories)
1.
2.
3.
Passive transfer of HLA or granulocyte antibodies that initiate an
inflammatory response in the pulmonary microvasculature
Granulocyte priming by biologically active substances such as lipids and
cytokines in the transfused plasma
Granulocyte priming as above followed by activation by transfused
antibodies (“two-event” hypothesis)
DEFINITION
Definite TRALI: New onset ALI within 6h of transfusion with no other
risk factors for ALI
Possible TRALI: New onset ALI within 6h of transfusion with one or
more risk factors for ALI
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Lamarche
TRANSFUSION-RELATED ACUTE
LUNG INJURY
Clinical presentation
Dyspnea, hypoxia, fever, hypotension, and leukopenia
Bilateral infiltrates with normal CVP, PCWP, and BNP
Usually occurs with RBC, FFP and platelet transfusions, but can rarely
occur with IVIG and cryoprecipitate
Almost always occurs within 1-2h after starting the transfusion
Usually resolves in 24-72 hours
*Criteria for ALI:
PO2:FiO2 < 300
PCWP <= 18
Bilateral chest infiltrates
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SEPSIS
Usually occurs during or within an hour of transfusion but can be
seen up to 4 or 8 h post transfusion
Incidence of symptomatic septic reactions:
Platelets 1:10 000 (stored at 20-24 degrees)
RBCs 1:100 000
Mortality
Platelets 1:40 000
RBCs 1:500 000
Etiology
Contamination of blood components by donor skin plug, bacteremic
donor, or improper handling of the blood product
Clinical presentation
Rigors, fever, tachycardia, hypotension, nausea and vomiting, dyspnea,
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DIC
DELAYED HEMOLYTIC TRANSFUSION
REACTION
Occurs from 2 to 14 days post transfusion
Incidence 1:4000 to 1:11 000
Etiology
Anamnestic antibody response in a patient with previously formed
antibodies (from prior transfusion, pregnancy, or transplant) that were
undetectable on pre-transfusion screening
Clinical presentation
Extravascular, gradual hemolysis with a falling Hb, slight fever, mild
unconjugated hyperbilirubinemia, low haptoglobin, elevated LDH, and
spherocytosis.
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POST-TRANSFUSION PURPURA
Occurs 5 to 10 days post transfusion
Incidence is unknown; ~300 cases have been reported.
Five (or 26) times more common in women then in men
Etiology
Delayed transfusion reaction to platelets in patients who have been
sensitized from prior transfusions or pregnancy (human platelet antigen
1a)
Clinical presentation
Severe thrombocytopenia (plts often < 10 000) that lasts days to weeks
8% mortality - most often secondary to an intracranial hemorrhage
Should be considered when a platelet refractory patient fails to respond
to HLA-matched platelets
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Lamarche
Transfusion-associated graft-versus-host
disease
Occurs 2 to 30 days post transfusion (most commonly between 4 and 10d)
Incidence: 1:400 000
Mortality: 80-90%
Etiology
Donor lymphocytes attack recipient’s lymphoid tissues (skin, liver, GI
tract, bone marrow); occurs in two settings:
1.
2.
Immunosuppressed pt cannot mount a response against donor
lymphocytes which then mount a response against the recipient
Recipient is heterozygous for an HLA haplotype for which the donor is
homozygous (recipient does not recognize the donor lymphocytes as
foreign. These then mount a response against the recipient.)
Clinical presentation
Fever, rash, liver dysfunction, and diarrhea, followed by pancytopenia
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Diagnosis made by skin, liver, or bone marrow biopsy
TRANSFUSION-TRANSMITTED
DISEASES
VIRAL:
HBV, HCV, HAV, HIV 1 & 2, HTLV 1 & 2, CMV, West Nile Virus
BACTERIAL (see sepsis)
Syphilis - no reported US cases since the 1960s
PARASITIC:
Malaria, babesia, chagas,
OTHER:
CJD, vCJD
Yoan
Lamarche
Yoan
Lamarche
Copyright ©2007 Canadian Medical Association or its licensors
REFERENCES
Bakdash S, Yazer MH. What every physician should know about transfusion reactions.
CMAJ. July 17, 2007; 177(2):141-147
Callum JL, Pinkerton PH. Bloody easy: A guide to transfusion medicine. 1st ed. Toronto:
Sunnybrook & Women's College Health Sciences Centre Press, 2003.
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Complications of transfusions
– ABO mismatch (#1 cause of death post
Transfusions)
– Hepatitis (#2)
– TRALI (#3)
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•
TRALI
– Criteria: transfusion- bilateral pulmonary infiltrates- low filling pressuresaProtein/pProtein > 0.75
– Causes
• Two-hit hypothesis
–
Recent surgery, sepsis, trauma, massive transfusions, hematologic
malignancies, and cardiac disease can all predispose
– Parity of the blood donor(1 RCT), relationship to the blood donor (Ab against
father), and the age of the blood products
• Bioactive lipids
– LysoPhosphatidylcholine: priming of neutrophils
– Would require cellular products transfusion
– TRALI has also been associated with FFP transfusion...
• Antibodies ± WBC
– Ab from donor interacts with recipients ± donor’s neutrophils and creates ALI
• CD40 Ligand: also implicated as a potential cause of pulm. transf reactions
– Prognosis: good: 5-10% mortality-clears in 24-48h
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The patient deteriorates further and you
notice the previous central line site is
now bleeding, as is your new femoral
central line.
18.How do you diagnose DIC? What
are the treatment strategies for the
patient presenting DIC? (Scot)
Yoan
Lamarche
Yoan
Lamarche
• Diagnosis – acute DIC;
– Suggested by: Hx (eg. Sepsis, trauma,
malignancy), thrombocytopenia (< 100,000), and
the presence of microangiopathic changes on
smear.
– Clinical manifestations:
•
•
•
•
•
•
•
Bleeding (64 percent)
Renal dysfunction (25 percent)
Hepatic dysfunction (19 percent)
Respiratory dysfunction (16 percent)
Shock (14 percent)
Thromboembolism (7 percent)
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Central nervous system involvement (2 percent)
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Peripheral blood smear from a patient with a microangiopathic
hemolytic anemia with marked red cell fragmentation. The smear
shows multiple helmet cells (small black arrows), other fragmented
red cells (large black arrow); microspherocytes are also seen (blue
arrows). The platelet number is reduced; the large platelet in the
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center (red arrow) suggests that the thrombocytopenia is due to
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enhanced destruction. Courtesy of Carola von Kapff, SH (ASCP).
• Dx confirmed by tests showing increased
thrombin generation (decreased fibrinogen),
and increased fibrinolysis (elevated D-dimer
and FDPs).
– Degree of abnormality correlates with overall
organ involvement and mortality.
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DIC - managment
• the management of DIC is based on the treatment of
the underlying disease, supportive and replacement
therapies and the control of coagulation mechanisms.
• Hemodynamic support is essential.
• Many patients do not require specific therapy for the
coagulopathy associated with DIC, either because it
is of short duration or because it is not severe
enough to present a major risk of bleeding or
thrombosis.
• There is no evidence to support the administration of
platelets and coagulation factors in patients who are
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not bleeding or who are not at high risk of bleeding.
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• Treatment with platelets and coagulation factors is
justified in patients who have serious bleeding, are at
high risk for bleeding (eg, after surgery), or require
invasive procedures. Patients with marked or
moderate thrombocytopenia (<50,000/microL) and
serious bleeding should be given platelet transfusions
(1 to 2 units per 10 kg per day).
• Actively bleeding patients with a significantly elevated
prothrombin time (INR) and/or a fibrinogen
concentration <50 mg/dL, should receive fresh frozen
plasma or cryoprecipitate in order to keep the
fibrinogen level >100 mg/dL.
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• The administration of heparin is
generally limited to the subset of
patients with chronic, compensated DIC
who have predominantly thrombotic
manifestations. It is important to be
sure that the patient's antithrombin
(AT) level is near normal (ie, 80 to 100
percent) in order for heparin to be
effective.
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• The usual intravenous bolus heparin injection of 5000
to 10,000 units should be avoided. One may start
with an IV dose of 500 units per hour, aiming for an
aPTT of about 45 sec. If the patient's baseline aPTT
is prolonged, the situation is more difficult, and one
aims for further slight prolongation of the aPTT.
• Once there is evidence of heparin effect, replacement
therapy with fresh frozen plasma or cryoprecipitate is
pursued. In chronic DIC, a continuous infusion can be
used, beginning at 500 units/hour. Low molecular
weight heparins are also efficacious.
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Lamarche
Thank You
Yoan
Lamarche