Transcript Anesthetic management of patients with hematological diseasex

Saad A. Sheta
MBBCH, MA, MD
Associate Professor,
Consultant Anesthesiologist
KSU
Evaluation of coagulation
Basic Hemostatic
Mechanisms:
I. Primary hemostasis
 Defects in primary hemostasis
von Willebrand’s disease
Thrombocytopenia
Acquired platelets function disorders
II. Coagulation
 Defects in coagulation
• Hemophilia
• Acquired factors deficiency
liver disease
Vit. K deficiency
Anticoagulant therapy
Heparin
Oral Anti- coagulants
Massive Blood Transfusion
DIC
III. Fibrinolysis
EVALUATION OF COAGULATION
 Laboratory testing is almost always needed to establish the
cause of bleeding
 Screening tests (PT, PTT, platelet count) will often allow
placement into one of the broad categories
 Specialized testing is usually necessary to establish a
specific diagnosis





Platelet Count
Bleeding Time (BT)
Prothrombin Time (PT)
Partial Thromboplastin Time (PTT)
Thrombin Time (TT)
NORMAL
100,000 - 400,000 cells/mm3
(100 – 400 x 10 9/L)
< 100,000
50,000 - 100,000
< 50,000
Thrombocytopenia
Mild Thrombocytopenia
Severe Thrombocytopenia
Provides Assessment Of Platelet Count And
Function

5-10% of patients have a prolonged bleeding time

Most of the prolonged bleeding times are due to aspirin or drug
ingestion

Prolonged bleeding time does not predict excess surgical blood loss

Not recommended for routine testing in preoperative patients
Normal Value
2-8 Minutes
COAGULATION FACTORS
Fibrinogen
II. Prothrombin
III. Tissue Thromboplastin
IV. Ca++
V. Labile Factor
VI. --------Unassigned
VII.Stable Factor
VIII.Anti hemophilic Factor
IX. Christmas Factor
X. Stuart Prowers factor
XI. Plasma Thromboplastin Antecedent
XII.Contact Factor
XIII.Fibrin Stabilizing Factor
I.
Partial thromboplastin time (PTT)
Prothrombin time (PT)
Phospholipid
(provided by platelet
which expose platelet F
III when they activated
Thromboplastin
Tissue factor
Phospholipids
Calcium
Normal Value
10-15 Sec
Normal Value
25 - 40 Sec.
Extrinsic pathway
Intrinsic pathway
Common pathway
Normal Value
9- 13 Sec.
Thrombin
Thrombin time
Fibrin clot

By-passes factors II-XII

Measures rate of fibrinogen conversion to fibrin

Procedure:
Add thrombin with patient plasma
Measure time to clot

Variables:
Source and quantity of thrombin
CBC and smear
Platelet count
RBC and platelet morphology
Thrombocytopenia
TTP, DIC, etc.
Coagulation
Prothrombin time
Partial Thromboplastin time
Coagulation factor assays
50:50 mix
Fibrinogen assay
Thrombin time
Extrinsic/common pathways
Intrinsic/common pathways
Specific factor deficiencies
Inhibitors (e.g., antibodies)
Decreased fibrinogen
Qualitative/quantitative
fibrinogen defects
Fibrinolysis (DIC)
FDPs or D-dimer
Platelet Function
von Willebrand factor
Bleeding time
Platelet function analyzer (PFA)
Platelet function tests
vWD
In vivo test (non-specific)
Qualitative platelet disorders
and vWD
Qualitative platelet disorders
Sex-linked recessive
Factors VIII and IX deficiencies cause bleeding
 Prolonged PTT; PT normal
Autosomal recessive (rare)
Factors II, V, VII, X, XI, fibrinogen deficiencies cause
bleeding
 Prolonged PT and/or PTT
Factor XIII deficiency is associated with bleeding and
impaired wound healing
 PT/ PTT normal; clot solubility abnormal
Factor XII, pre-kallikrein, HMWK deficiencies
 No bleeding
Platelet disorders
Coagulation factor disorders
Site of bleeding
Skin
Mucous membranes
(epistaxis, gum,
vaginal, GI tract)
Deep in soft tissues
(joints, muscles)
Petechiae
Yes
No
Ecchymoses (“bruises”)
Small, superficial
Large, deep
Hemarthrosis / muscle bleeding
Extremely rare
Common
Bleeding after cuts & scratches
Yes
No
Bleeding after surgery or trauma
Immediate,
usually mild
Delayed (1-2 days)
often severe
Basic Hemostatic Mechanisms
I.
II.
III.
Primary hemostasis
Coagulation
Fibrinolysis
Basic Hemostatic
Mechanisms
I.
Primary hemostasis
Blood Vessel Spasm
 Cutting or breaking smaller vessels stimulates the
smooth muscles in its walls to contract. May close
completely
 Effects last only a few minutes to 30 minutes
 Platelets release serotonin which stimulates
vasoconstriction and helps maintain vessel spasm
1. Platelets Activation
2. Platelets Adherence
von Willebrand factor (intracellular glue ; stick platelets to collagen)
3. Activated platelets release of chemical products
ADP, Serotonin, Platelet factor IV(ca++) , B thromboglobin,
fibronectin, vWF, fibrinogen, factor V, labile factor,….
4. PG , called Thromboxane A2 is released
Further ADP further aggregation
potent vasoconstrictor
5.
Aggregated platelets:
trap thrombin (coagulation cascade)
trap plasminogen platelet plug temporary arrest bleeding
6. larger break may require a blood clot to halt bleeding
In case of intact endothelium, Prostacyclin . PG its action
opposite to Thromboxane A2
non-thrombogenic
Quantitative disorders
Inherited disorders (vWF)
rare
Qualitative disorders
Acquired disorders
 von Willebrand’s disease
Inherited / Qualitative ± (Quantitative)
 Thrombocytopenia
Quantitative
 Acquired platelets function
disorders
Qualitative
von Willebrand factor





Synthesis in endothelium and megakaryocytes
Forms large multimer
Carrier of factor VIII
Anchors platelets to sub endothelium
Bridge between platelets
Inheritance - autosomal dominant
Incidence - 1/10,000
Clinical features - mucocutaneous bleeding
Classification:
Type 1
Type 2
Type 3
Partial quantitative deficiency
Qualitative deficiency
Total quantitative deficiency
Diagnostic tests:
Assay
vWF antigen
vWF activity
Multimer analysis
1
von Willebrand type
2
3
Normal
Normal
Normal
Absent
Cryoprecipitate


Source of fibrinogen, factor VIII and vWF
Only plasma fraction that consistently contains VWF multimers
DDAVP (deamino-8-arginine vasopressin)
 plasma vWF levels by stimulating secretion from endothelium
 Duration of response is variable
 Not generally used in type 2 disease
 Dosage 0.3 µg/kg q 12 hr IV

Factor VIII concentrate (Intermediate purity)

Virally inactivated product
 Decreased production
(bone marrow)
 Increased sequestration
(spleen)
 Dilutional
(massive blood transfusion)
 Consumption
( burn, pre- eclampsia, DIC, CPB)
 Immune
(heparin)
Immune-mediated
thrombocytopenia (ITP)
Features
Acute ITP
Chronic ITP
Peak age
Female : male
Antecedent infection
Onset of symptoms
Platelet count at presentation
Duration
Spontaneous remission
Children (2-6 yrs)
1:1
Common
Abrupt
<20,000
2-6 weeks
Common
Adults (20-40 yrs)
3:1
Rare
Abrupt-indolent
<50,000
Long-term
Uncommon
History
 Is the patient bleeding?
 Are there symptoms of a secondary illness? (neoplasm,




infection, autoimmune disease)
Is there a history of medications, alcohol use, or recent
transfusion?
Are there risk factors for HIV infection?
Is there a family history of thrombocytopenia?
Do the sites of bleeding suggest a platelet defect?
Assess the number and function of platelets
 CBC with peripheral smear
 Bleeding time or platelet aggregation study
Platelet count
(per µl)
Symptoms
Treatment
> 50,000
None
None
20-50,000
No bleeding
Bleeding
None
Glucocorticoids
iv -IG
< 20,000
No bleeding
Bleeding
Glucocorticoids
Glucocorticoids
iv - IG
Hospitalization
Uremia
Guanidino succuinic a. toxic to platelets
Alcohol
Cirrhosis
Medication s:
Aspirin (indomethacin, phenylbutazone, ibuprofen, dextran)
inhibit the synthesis of thromboxane A2 (Aspirin for 16-24 hrs)
FDP
Basic Hemostatic Mechanisms
II.
Coagulation
Most effective hemostatic mechanism
Causes formation of a blood clot
Clotting factors:
 Biochemicals (Plasma Protein) that promote or inhibit coagulation
 Whether or not blood coagulates depends on the balance between
2 groups of factors
Normally, anticoagulants prevail = no clots
Following injury, Biochemicals that favor coagulation may increase and blood
coagulates
Fibrinogen
II. Prothrombin
III. Tissue Thromboplastin
++
IV. Ca
V. Labile Factor
VI. --------Unassigned
VII. Stable Factor
VIII. Anti hemophilic Factor
IX. Christmas Factor
X.
Stuart Prowers factor
I.
XI.
Plasma Thromboplastin Antecedent
Contact Factor
XIII. Fibrin Stabilizing Factor
XII.
Vit. K dependent Coagulation Factors
Factors V & VIII
 Can not stay in the storage blood
 Don not become active cleavage
(serve as co-factors)
Factor VIII (Extra hepatic, MW 400,000 )
VIII C
Smaller
Hemophilia A
VIII R Ag
Larger
Hemophilia A
+ vWF
Separate genetic control
Intrinsic system (surface contact)
Extrinsic system (tissue damage)
Contact Factor
XII
XII a
Tissue factor
Pl..Thromboplastin Antecedent
XI
XI a
Christmas Factor
IX
IX a
VIII
VII a
Stable Factor
VII
VIII a
Xa
Stuart Prowers Factor
X
V
Prothrombin
II
Fibrinogen
Va
II a
Thrombin
Fibrin
 Prothrombin activator: damaged tissue signals this
to be produced
 Prothrombin (Factor II) : α globulin (liver) It is
converted to thrombin by:
Prothrombin activator
++
Ca
 Thrombin catalyzes a reaction that fragments
fibrinogen
 Long fibrin threads stick to exposed surfaces of
damaged blood vessels creating a meshwork that
entraps blood cells and platelets
 Resulting mass is a blood clot which may block a
vascular break and prevent further blood loss
The major event in blood clot formation is the conversion of:
soluble fibrinogen (a plasma protein) into insoluble threads of
fibrin
Serum: clear, yellow fluid that remains after clot
Same as plasma, minus the clotting factors
Normally:
 Blood flow prevents massive clot formation within the
cardiovascular system by rapidly carrying excess thrombin
away, keeping its concentration too low to enhance further
clotting
 Blood coagulation is usually limited to blood standing still or
moving slowly. Clotting ceases where clot contacts circulating
blood
Abnormal Clot Formations
Thrombus: a clot abnormally forming in a vessel
Embolus:
 If a clot dislodges or if a fragment of it breaks loose and is
carried away by blood flow
 Continues to move until it reaches narrow place in vessel where
it may lodge and block flow
Often associated with conditions that change endothelial
lining of vessels. e.g. Atherosclerosis = accumulations of
fatty deposits
Artery cross sections. A.) Light micrograph of a normal artery. B.) Thinner
wall of this artery changed as a result of atherosclerosis

Hemophilia
 Acquired factors deficiency
liver disease
Vit. K deficiency
Anticoagulant therapy
Heparin
Oral Anti- coagulants
Massive Blood Transfusion
DIC
Hemophilia
Hemophilia A
Coagulation factor deficiency
Inheritance
Incidence
Hemophilia B
Factor VIII
X-linked
recessive
1/10,000 males (80-85%)
Factor IX
X- linked
recessive
1/50,000 males (10-15%)
SEVERITY RELATED TO FACTOR LEVEL
< 1%
- Severe - spontaneous bleeding
1-5% - Moderate - bleeding with mild injury
5-25% - Mild - bleeding with surgery or trauma
LAB:
PROLONGED
PTT
COMPLICATIONS :
Soft tissue bleeding
Clinical manifestations
Hemophilia A & B are indistinguishable
Hemarthrosis (most common)
Fixed joints
Soft tissue hematomas (e.g., muscle)
Muscle atrophy
Shortened tendons
Other sites of bleeding
Urinary tract
CNS, neck (may be life-threatening)
Prolonged bleeding after surgery or dental extractions
Depends upon
 Type of surgery
 The level of native factors (VIII &IV)
 Half life of infused factors
 Hematologist consultation in case of massive bleeding

Intermediate purity plasma products
Virucidally treated
May contain von Willebrand factor

High purity (monoclonal) plasma products
Virucidally treated
Non functional von Willebrand factor

Recombinant factor VIII
Virus free/No apparent risk
Non functional von Willebrand factor

Mild bleeding
Target: 30% dosing q8-12h; 1-2 days (15U/kg)
Hemarthrosis, oropharyngeal or dental, epistaxis, hematuria

Major bleeding
Target: 80-100% q8-12h; 7-14 days (50U/kg)
CNS trauma, hemorrhage, lumbar puncture
Surgery
Retroperitoneal hemorrhage
GI bleeding

Adjunctive therapy
-aminocaproic acid (Amicar) or DDAVP (for mild disease only)

Formation of inhibitors (antibodies)
10-15% of severe hemophilia A patients
1-2% of severe hemophilia B patients

Viral infections
Hepatitis B
Hepatitis C
HIV
Human parvovirus
Hepatitis A
Other
HIV -positive
(n=382)
53%
Negative
Hepatitis B virus only
Hepatitis C virus only
Hepatitis B and C
HIV-negative
(n=345)
47%
1
1
24
74
20
1
45
34
Blood 1993:81;412-418
Agent
High purity factor IX
Recombinant human factor IX
Dose
Initial dose: 100U/kg
Subsequent: 50U/kg every 24 hours
Acquired factors deficiency
liver disease
Vit. K deficiency
Anticoagulant therapy
Heparin
Oral Anti- coagulants
Massive Blood Transfusion
DIC

Decreased synthesis of
II, VII, IX, X, XI, and fibrinogen
Since factor VIII of extrinsic pathway has the shortest 1/2 life, the onset of liver
dysfunction will initially prolong PT (later PTT &a PTT)

Dietary Vitamin K deficiency (Inadequate intake or
malabsortion)

Dysfibrinogenemia

Enhanced fibrinolysis (Decreased alpha-2-antiplasmin)

DIC

Thrombocytoepnia due to hypersplenism
Treatment for prolonged PT/PTT




Vitamin K 10 mg SQ x 3 days - usually ineffective
Fresh-frozen plasma infusion
25-30% of plasma volume (1200-1500 ml)
immediate but temporary effect
Treatment for low fibrinogen
Cryoprecipitate (1 unit/10kg body weight)
Treatment for DIC
(Elevated D-dimer, low factor VIII, thrombocytopenia)
Replacement therapy

Fat soluble vitamin
malnutrition → ↓ Vitamin k

Relies upon bile for proper absorption
biliary obstruction
malabsortion → ↓ Vitamin k

Intestinal flora play san important role in converting vitamin k
sterilization of the gut by antibiotics
Enema → ↓ Vitamin k

Anticoagulant (Coumodin) competing with the binding site at liver
Administration ↓ Vitamin k
Factors: II, VII, IX, X are vitamin K dependent
final step in their synthesis a carboxyl group is added to each clotting factor
Naturally occurring anticoagulant
Bearing a string negative charge
Acts via anti-thrombin III which binds to thrombin and prevents it from
converting fibrinogen to fibrin
Acts with other cleavage enzymes on the intrinsic and common pathways
Dosages:
DVT: 24-48,000 units/24hs (IV infusion)
Prophylaxis: 5000 units/8-12hrs → 7-10 days
Laboratory lest of choice: PTT should be 1.2-2.5 normal
Reversal Protamine sulphate :
slowly IV 1mg/100units heparin
More than 50 mg (anticoagulant ,flushing, bradycardia, hypotension)
Intrinsic system (surface contact)
Extrinsic system (tissue damage)
Contact
Factor
XII
XII a
Tissue factor
Pl..Thromboplastin Antecedent
XI
XI a
Christmas Factor
IX
IX a
Heparin →
VIII
VIII a
Heparin→
Xa
Stuart Prowers Factor
X
V
Va
II a
Prothrombin
II
Fibrinogen
Stable
Factor
VII
VII a
(-)
anti-thrombin
Thrombin
Fibrin
← Heparin
Dosage: 3-10mg daily
( → PT 2-4 x normal)
Vitamin K1 (Phytomenadione ) as effective orally, iv, im
Dosage in warfarin induced hemorrhage (or anticoagulant Over
dosage) 2.5-20 mg
Reversal takes 12 hours (vitamin k dependent dotting factors return to the plasma in order of
their ½ life) if surgery can’t wait → FFP
Permanent anticoagulant therapy (AF & value prosthesis )
→ heparin during the period of suspended oral anticoagulant in an
attempt to ↓ thromboembolic sequel e
5000 U of heparin/8-12hrs sc until warfarin is established
This sub-pharmacological dose does not cause bleeding during surgery
Clinical situation
Guidelines
INR therapeutic-5
Lower or omit next dose;
Resume therapy when INR is therapeutic
INR 5-9; no bleeding
Lower or omit next dose;
Resume therapy when INR is therapeutic
Omit dose and give vitamin K (1-2.5 mg po)
Rapid reversal: vitamin K 2-4 mg po (repeat)
INR >9; no bleeding
Omit dose; vitamin K 3-5 mg po; repeat as
necessary
Resume therapy at lower dose when INR
therapeutic
Chest 2001:119;22-38s (supplement)
Clinical situation
Guidelines
INR > 20; serious bleeding
Omit warfarin
Vitamin K 10 mg slow IV infusion
FFP or PCC (depending on urgency)
Repeat vitamin K injections
every 12 hrs as needed
Any life-threatening bleeding
Omit warfarin
Vitamin K 10 mg slow IV infusion
PCC
(or recombinant human factor VII a)
Repeat vitamin K injections
every 12 hrs as needed
Chest 2001:119;22-38s (supplement)

Crystalloid, albumin, hetastarch → dilution of clotting factors

Stored RBCs
 Dilutional Thrombocytopenia,
 ↓ Labile factors V &VIII
 DIC
PT & a PTT require only minimum 30% of normal coagulant activity of
any of the dotting factors, in order for these tests to be normal
Systemic activation
of coagulation
Intravascular
deposition of fibrin
Thrombosis of small
and midsize vessels
with organ failure
Depletion of platelets
and coagulation factors
Bleeding

Poor bleed flow:
Shock- hypotension , vascular occlusion
Poor blood flow allows: platelets to aggregate, expose factors, initiate
the intrinsic pathway of coagulation

Liver disease:
The diseased liver has a decreased ability to clear activated dotting
factors, as well as FDP
Releases thromboplastin into circulation → DIC.

Tissue thromboplastin
 massive crush injuries
 major strokes
 obstetric catastrophes
 Amniotic fluid embolus
 Abruptio placenta
 Fetal death


Presence of a phospholipid surface:
In the process if DIC, the diffuse circulation of phospholipids
throughout the blood steam, can produce so much thrombin that the
antithrombin Ш is overwhelmed

antithrombin Ш to limit & regular coagulation by binding to
thrombin & other active cleavage enzymes in the intrinsic pathway
The circulating phospholipids comes from TWO sources:
 Platelets can be activated throughout the blood stream by immune
complexes or even by bacteria ( e.g.. Septic Shock)
 Diffuse Platelet aggregation & activation may also develop in pts
who have large areas of denuded endothelium
 burn diffuse
 vacuities
 pre-eclampsia
Consumption of
coagulation factors;
presence of FDPs
Release of
thromboplastic
material into
circulation
Coagulation
Fibrinolysis
Fibrinogen
 a PTT
 PT
 TT
 Fibrinogen
Plasmin
Thrombin
Presence of plasmin
Fibrin
Monomers
 FDP
Fibrin(ogen)
Degradation
Products
Fibrin
Clot
(intravascular) Plasmin
Intravascular clot
 Platelets

Platelets are consumed

Fibrinolytic system fires up, Lyzing blood clots in an
attempt to maintain blood fluidity

Plasmin → FDP

If FDPs are produced at a faster rate than they can be cleared
→ anticoagulant effect
(normal half life 9hrs)
 (-) platelet aggregation
 Prevent the normal cross – linking of fibrin w is necessary to make a
lot insoluble

Blood flow, if compromised, should be improved by:
 Augmenting of CO
 Correction of acid
 Base disturbances

Source of the circulating phospholipids must be removed:
 ↓fibrinolytic activity
 ↓ FDP

Platelet transfusion

FFP , Fresh blood, specific Component

Heparin
(Questionable give additional time to treat cause )





High dose impairs hemostasis
Low dose: 15 U/kg 20 U/kg/hr for 24hrs
Platelet count & fibrinogen level
Heparin stopped or reduced
Amino coproic acid ( ACA )
not recommended
inhibit formation of plasmin → severe thrombo-embolic episodes
Prophylactic
Desmopression (DDAVP)
↓blood loss & transfusion requirements
Dipyridamol
limited platelet activation and aggregation
Basic Hemostatic
Mechanisms
III.
Fibrinolysis
Blood vessel spasm, platelet plug formation, and blood
coagulation provide homeostasis following tissue damage
Activation (endothelial damage)
Plasmin does not circulate in bl. stream as such
because anti-plasmin circulate in conc. 10 X that of
plasmin
Plasminogen
inactive
TPA
PLASMIN INHIBITORS
Its precursor (plasminogen) circulate in
bloodstream
As clot evolves, it incorporates the plasminogen &
an enzyme Called tissue plasminogen activator TPA
(which convert plasminogen to plasmin)
Plasmin
ENZYME FOR FIBRINOLYSIS
LYSIS FIBIN CLOT
Fibrin
Plasmin is produced within fibrin clot & shield from
antiplasmin
Then out of fibrin clot to blood
FDP

Anticoagulant
 Interfere with fibrin polymerization
 Metabolized by the liver
 Picked up with RES
Antiplasmin rapidly neutralize & prevent wide
spread uncontrolled fibrinolysis
 Excreted in kidney
Is the bleeding local or due to a hemostatic failure?

Local: Single site of bleeding usually rapid with
minimal coagulation test abnormalities

Hemostatic failure: Multiple site or unusual pattern
with abnormal coagulation tests
Evaluate for causes of peri-operative hemostatic failure

Preexisting abnormality

Special cases (e.g. Cardiopulmonmary bypass)
Diagnosis of hemostatic failure

Review pre-operative testing

Obtain updated testing
Identify and correct any specific defect of hemostasis
 Laboratory testing is almost always needed to establish the
cause of bleeding
 Screening tests (PT,PTT, platelet count) will often allow
placement into one of the broad categories
 Specialized testing is usually necessary to establish a specific
diagnosis
Use non-transfusional drugs whenever possible
RBC transfusions for surgical procedures or large blood loss
Definition
Anemia is operationally defined as a reduction in one or more
of the major RBC measurements:
Hemoglobin concentration
Hematocrit
RBC count
 Anemia is a sign, not a disease
 Anemias are a dynamic process
 Its never normal to be anemic
 The diagnosis mandates lab work-up
Etiology of Anemia
• Anemias due to DECREASED ERYTHROPOIETIN PRODUCTION
 Renal disease
 Endocrine deficiency (pituitary, adrenal, thyroid, testis)
 Starvation
 Hemoglobinopathy (reduced oxygen affinity)
• Anemias due to INADEQUATE MARROW RESPONSE TO ERYTHROPOIETIN
 Deficiency state (iron, vitamin B12, folate)
 Anemia of chronic disease
(inflammation, infection, or malignancy)
 Sideroblastic anemia
 Myelo-dysplasia
 Pure red cell aplasia
• ERYTHROCYTE LOSS
 Hemorrhage
 Hemolysis
ANEMIA
reticulocyte count
UNDERPRODUCTION
reticulocyte count
INCREASED DESTRUCTION OR
LOSS

Increased reticulocytes (greater than 2-3% or 100,000/mm3
total) are seen in
 Blood loss
 Hemolytic processes
25% of hemolytic anemia will present with a normal reticulocyte count due
to immune destruction of red cell precursors

Retic counts are most helpful if
extremely low (<0.1%)
 greater than 3% (100,000/mm3 total)

To be useful the reticulocyte count must be adjusted for the
patient's hematocrit
The hematocrit is lower reticulocytes are released earlier
from the marrow so one can adjust for this phenomenon.
Thus:
RC corrected = RC x (Hct /45)
Reticulocyte index (RPI) = RC corrected / Maturation time
(Maturation time = 1 for Hct=45%, 1.5 for 35%, 2 for 25%, and 2.5 for 15%.)
RPI = 1 : (N. non-anemic )
RPI < 2 : hypo proliferative
RPI > 2 : hyper proliferative
UNDERPRODUCTION
Low MCV
Normal MCV (110 – 115)
High MCV (>115)
MCV (femtoliters) = 10 x HCT(percent) ÷ RBC (millions/µ)
Microcytic Anemia
Normocytic Anemia
Macrocytic Anemia
Megaloblastic
B12/folate deficiency
 Iron deficiency
 Thalassemias
 Anemia of chronic dz
 Sideroblastic
Pan cytopenias
 Red cell aplasia
 Anemia of chronic dz
 Sideroblastic
Non-megaloblastic
 liver dz
 Hypothyroid
 Drugs that impair
DNA synthesis
 Aplastic anemia
 Sideroblastic
INCREASED DESTRUCTION OR LOSS
LDH
Bilirubin
Haptoglobin
Hemolysis







G6PD deficiency
Sickle cell
Hereditary spherocytosis
Autoimmune hemolytic anemia
Drug-induced
Hypersplenism
DIC, TTP, HUS
Acute Blood Loss

↓ Red cell mass → ↑ plasma vol. to preserve blood
volume

ODC → Right (Hb molecules less avid for O2 at any
given PP to improve oxygenation) via ↑ 2,3 DPG
↑ Stroke volume
↑ Heart rate

Maintenance of O2 delivery in anemia is dependent
upon ↑ CO & Hb %

Hb is an important buffer for CO2 induced pH change

ODC will be adversely affected by hypocapnia (←
to the left)

Transfused Hb has 70% of normal 2,3 DPG level &
there are unload O2 poorly → 24hrs is required to
restore 2,3 DPG to normal level
Key questions in history
 Is there evidence of bleeding?
 Duration
 Ethnicity
 Medications
Physical exam
 Jaundice
 Lymphadenopathy, HSM, bone tenderness
 Other signs of heme abnormalities
Hemolytic Anemias
Hemolytic anemias are either acquired or congenital.
The laboratory signs of hemolytic anemias include:
 Increased LDH (LDH1)
 Increased indirect bilirubin
sensitive but not specific
sensitive but not specific
 Increased reticulocyte count
 Decreased haptoglobin
 Urine hemosiderin
specific but not sensitive
specific but not sensitive
specific but not sensitive
The indirect bilirubin is proportional to the hematocrit, so with a hematocrit
of 45% the upper limit of normal is 1.00 mg/dl and with a hematocrit of
22.5% the upper limit of normal for the indirect bilirubin is 0.5mg/dl
Since tests for Hemolysis suffer from a lack of sensitivity and specificity,
one needs a high index of suspicion for this type of anemia
Avoid drugs that trigger hemolytic crisis
Non opioid analgesics
Antibiotics
Sulphonamide
Avoid drugs that associate with met Hb
Prilocaine
nitrupusside
A Hemoglobinopathy with
autosomal-dominant inheritance


Homozygote: Sickle cell Disease
(2 abnormal genes)
Synthesize no Hb A
RBCs contain 90-100% Hb S
Heterozygotes: Sickle cell trait
(1 abnormal gene)
RBCs contain 20-40% Hb S

*Hb-S :  globin gene mutation   Valine substitute Glutamic acid

*Deoxygenation
Valine translocated from position 6 to an external position interact
with other hydrophobic elements within neighbouring globulin chain
insoluble globin polymers  sickling
Deoxygenation of SS erythrocytes leads to intracellular
hemoglobin polymerization, loss of deformability and
changes in cell morphology
OXYG - STATE
DEOXYG -STATE

Hb-S has different electrohporetic mobility (higher net
electric charge)

Deoxygenated Hb-S is less soluble, forming rod-like
tactoids, distort RBC Sickle form


Sickle cells prematurely destroyed hemolytic anemia
Sickle cells cause increased blood viscosity impaired
blood flow initiate thrombosis
A) Deoxy-hemoglobin S
B) Paired strands of
14-stranded polymer
(electron micrograph)
deoxy-hemoglobin S
(crystal structure)
C) Hydrophobic pocket
for 6b Val
D) Charge and size prevent
6 Glu from binding
Dykes, Nature 1978; JMB 1979
Crepeau, PNAS 1981
Wishner, JMB 1975
1- Oxidative damage to cell membrane
2- Poor deformability of RBCs
Sickling
3- RBCs become prone to dehydration
 prematurely removed by RES 
Hemolysis
Infarction
 abnormal adhesion to
endothelial cells 
Vaso-occlusion

Vaso-occlusion Hypoxia
Sickling  tissue
infarction….Cytokines  Pain
more
Local
Hypoxia&
acidosis
Micro
vascular
Blood
Flow
A- Hemolysis
B- Vaso-occlusion
•








(RBCs survival)
*Anemia.
*Jaundice.
*Gall stones.
*CHF.
*Leg ulcers.
Bone marrow hyperplasia
(Dysmorphic features).
Delayed growth ( BW)
•
•
•
•
Painful crisis (bone ,
muscle)
Acute chest syndrome.
CV stroke
Eye damage.
Functional hypo-splenism
or auto-splenectomy
C- Organ dysfunction
LOCAL INFARCTIONS CAUSE THE CLINICAL PICTURE OF SICKLE CELL
CRISIS
Problems:

ANEMIA

CRISIS & PREVENTION

PRE-EXISTING ORGAN DAMAGE

SURGICAL PROCEDURE ( SICKLE RELATED )

INFARCTION RISK
PREOPERATIVE ASSESS & PREMEDICATION
I.
Diagnosis
II.
Transfusion Therapy
III. Fasting
Limited
I.
Assess organ damage
II.
Sedation
Over-sedation should be avoided
Preoperative Assess & premedication
I.

Diagnosis
CBC :
Irreversibly sickled cell, target cells
- Anemia, reticulocytosis
- leukocytosis
- Thrombocytosis
-  ESR
-  Bilirubin (indirect)
-


Electrophoresis
Hb-S (with acidification)
Solubility test (Ethnic Group)
(adding reducing agent : 2% sodium Meta- bi-sulfate)
Hb ppt if Hb-S > 15%
Preoperative Assess & premedication
II. Transfusion Therapy

Mechanisms
 Simple transfusion – give blood
 Partial exchange transfusion - remove blood and give blood
 Erythrocytapheresis – use aphaeresis to maximize blood exchange

Preoperative blood transfusion is considered to be a standard practice to
maintain Hb
 > 10 gm/dl (intermediate or high risk)
 Hb A > 40)%
 For minor procedures , is no need for transfusion

Transfusion Therapy
 Used correctly  prevent organ damage
 Used unwisely  serious complications.
New England Journal of Medicine. 1995 ;333 :206-13

There no difference in the outcome in patients undergoing minor
surgery
 whether the Hb-S is reduced to (30-34%)
or
 Hb is maintained around 10 gm/dl

Operative Hb-S levels has little correlation with the anesthetic
management for SCD patients
BJA 1998 ;80 :820-28
IF THE PATIENT IS STABLE AND THE RETICULOCYTE COUNT HIGH,
TRANSFUSIONS CAN (AND SHOULD) BE DEFERRED






Chronic steady-state anemia
Uncomplicated pain episodes
Infection
Minor surgery
Uncomplicated pregnancies
A septic necrosis

In severely anemic patients, simple transfusions should be used

Common causes of acute anemia:
 acute splenic sequestration
 transient red cell aplasia
 Hyper-hemolysis
(infection, acute chest syndrome, malaria)


In general, patients should be transfused if there is sufficient physiological
derangement to result in heart failure, dyspnea, hypotension, or marked
fatigue
Tends to occur during an acute illness or when hemoglobin falls under 5 g/dL.
EXCHANGE TRANSFUSION:



Bleed One Unit (500 Ml), Infuse 500 Ml Of Saline
Bleed A Second Unit And Infuse Two Units
Repeat. If The Patient Has A Large Blood Mass, Do It
Again
BENEFITS (FIRST CHOICE)



Phenotypically Matched, Leuko-depleted Packed Cells
A Post-transfusion Hematocrit Of 36 Percent Or Less
Avoid Hyper Viscosity
A COMPREHENSIVE TRANSFUSION PROTOCOL SHOULD INCLUDE
ACCURATE RECORDS OF :





The Patient’s Red Cell Phenotype
Allo-immunization
History, Number Of Units Received
Serial Hb S Percentages
Results Of Monitoring For Infectious Diseases And Iron
Overload.
Transfusions Usually Fall Into Two Categories:
EPISODIC, ACUTE TRANSFUSIONS TO STABILIZE OR REVERSE COMPLICATIONS

Limited studies have shown that aggressive transfusion (get Hb S <
30%) may help in sudden severe illness

May be useful before general anesthesia
LONG-TERM, PROPHYLACTIC TRANSFUSIONS TO PREVENT FUTURE
COMPLICATIONS
CONTROVERSIAL USES:
Prior to contrast media exposure
Sub-clinical neurological damage
Priapism
Leg Ulcers
Pregnancy
CONDUCT OF ANESTHESIA
PRIME CONCERNS
AVOID 5 HS:





HYPOXIA
Hypothermia
Hypovolemia
Hypercarpia
Hypotension
ADEQUATE ANALGESIA
CONDUCT OF ANESTHESIA
OTHER CONCERNS

FIO2
 MONITORING
 POSITIONING CAREFUL
 AVOID TOURNIQUET
 VENTILATE TO MILD RESPIRATORY ALKALOSIS
 AVOID BIER’S BLOCK
POSTOPERATIVE
HDU

OXYGEN CHEST PHYSIOTHERAPY

HYDRATION

AVOID THE 5HS

EARLY AMBULATION

INFECTION IS A PARTICULAR RISK

ANALGESIA