Transcript Anemia

ANEMIAS
Mohammad Abu-Fara. MD
ANEMIA
Anemia: Is defined as a reduction in one or more
of major RBC measurements.
HGB.
HTC.
RBC count .
Anemia is not a disease by itself but is one of
the major signs of disease.
May be the first manifestation of a systemic
disease, along with other nonspecific complaints
such as fever, weight loss, anorexia.
HGB Concentration: measures the major
oxygen-carrying pigment in whole blood.
Values are expressed as grams of HGB per
dL of whole blood (g/dL).
The normal ranges for HB. Varies in men
and women and in different age group.
Normal range: M 13-16,5 g/dL
F 12-15,5 g/dL
Hematocrit (HTC): Is the percent of a
volume of whole blood occupied by intact
RBCs.
Values are expressed as a percentage.
Normal range: M 41-51%.
F 37-47%.
RBC Count: Is the number of RBCs
contained in a unit of whole blood.
Values are expressed as millions of cells per
uL of whole blood.
Normal range: M 4,5-6,5
F 3,8-5,8
VOLUME STATUS
The three measurements are all
concentrations.
As such they are dependent upon both the
RBC mass and the plasma volume.
1.In acute bleeding anemia develops only
after 36-48 hours.
2.Pregnancy:RBC mass is increased by 25%
and plasma is increased by 50%.Normal
values in pregnancy are different.
3.Dehydration.
SPECIAL POPULATIONS
1.Living at high altitude.
2.Smoking and air pollution.
3.African-Americans—lower values.
4.Populations with a high incidence of ch.
diseases.
5.Athletes.
6.The elderly: should not have a lower
normal range for fear of missing a serious
underlying disorder.
ERYTHROPOESIS
The rate of RBC production equals the rate
of RBC destruction.
Approximately 1% of RBCs is removed from
the circulation daily.
The rate of RBC production can increase
markedly under the influence of high
levels of EPO.5-7 folds.
CLINICAL CONSEQUENCES OF
ANEMIA
The signs and symptoms induced by anemia
are dependent upon the degree of anemia
as well as the rate at which the anemia
has evolved.
Symptoms of anemia can result from two
factors:
1.Decreased O2 delivery to tissues.
2.Hypovolemia/acute blood. loss/.
COMPENSATORY
MECHANISMS
Signs and symptoms depend also on the
compensatory mechanisms.
1.Extraction of O2 by the tissues can increase
from 25% to 60%.
2.Cardiac compensation :stroke volume and heart
rate/cardiac output/.
Thus normal O2 delivery can be maintained by 1
and 2 at rest at HBG as low as 5g/dL,assuming
that the intravascular. volume is maintained.
Thus symptoms will develop when HBG falls below
this level at rest or at higher HBG during
exertion or when cardiac compensation is
impaired.
SYMPTOM AND SIGNS
Symptom :is a sensation or change in
health function experienced by the
patient. It is a subjective report.
Dyspnea /S.O.B. :on exertion/at rest.
. Fatigue/tiredness.
Signs and symptoms of hyperkinetic state:
1.bounding pulses.
2.palpitations.
3.roaring in ears.
In more severe anemia: Lethargy, confusion, CHF,
angina, MI., Pallor.
Headache.
Visual impairment, syncope
Complications of extra cellular volume depletion/in
acute bleeding/
Symptoms and sign due to the underlying cause of
anemia .
Iron deficiency
Most cases are caused by menstrual loss and increased
iron requirements of pregnancy.
GI bleeding is the presumed etiology in most patient 
Decreased iron absorption (celiac disease, 
postgastrectomy, or increase iron requirement as in
lactation.
History of pica (consmption of substances such as ice,
starsh or clay ) can be obtained .
Signs : splenomegaly, kiolonychia (spoon nail ) and 
plummer- vinson syndrome (glossitis, dysphagia, and
esophageal webs) are rare finding.



Vitamin B12 and Folate deficiency
Glossitis, angular stomatitis, juandice,
splenomegaly and neurological syndrome
of pernicious anemia ( subacute combined
degeneration-demylination of dorsal and
lateral columns of spinal cord. unsteady
gait and progress to irreversible damage
and bladder disturbance (only in VB12
def.)
Sign: is an objective evidence of the
presence of a disease or disorder .Signs
are discovered and reported
by the physician, not by the patient.
Elevated BP.
Skin rash.
Tachypnea.
CAUSES OF ANEMIA
There are 2 interrelated approaches one can
use to help identify the cause of anemia.
1.Kinetic approach.
2.Morphologic approach.
KINETIC APPROACH
Anemia can be caused by one or more of 3
independent mechanisms.
1.Decreased RBC production.
2.Increased RBC destruction.
3.RBC loss.
MORPHOLOGIC APPROACH
According to RBC size.
Mean Corpuscular Volume /MCV/.
RBC size/MCV/ is 80-96 femtoliters(fL).
Microcyte.
Macrocyte.
Normocyte.
ANEMIAS ACCORDING TO THE
RBC SIZE
1.Microcytic anemia.
2.Macrocytic anemia.
3.Normocytic anemia.
MICROCYTIC ANEMIAS
Are associated with an MCV below 80 fL.
IDA
ACD
Thalassemias.
MACROCYTIC ANEMIAS
Are characterized by an MCV above 100 fL.
Reticulocytosis.
Vit.B12 def.
Folate def.
MDS.
Liver disease
Hypothyroidism
NORMOCYTIC ANEMIAS
By definition the MCV is normal.
ACD.
MDS.
EVALUATION OF THE PATIENT
WITH ANEMIA-1
Anemia is one of the major signs of disease.

It is never normal and it's cause should be
always be sought.

History.

Physical examination.

Simple lab. tests.
Are all useful in evaluating the anemic patient.

EVALUATION OF THE ANEMIC
PATIENT-2
The workup should be directed towards
answering the following questions:
1.Is the patient bleeding (now or in the past)
?.
2.Is there evidence of increased RBC
destruction?
3.Is the BM suppressed?.
4.Is the patient iron deficient?if so,why?.
Anemia associated with red blood
cell loss or destruction
Sickle cell disease 
G6PD deficiency 
Hemolytic anemia 
BLEEDING
DISORDERS
HEMOSTASIS-1
In health hemostasis ensures that the blood
remains fluid and contained in the vascular
system.
 If a vessel wall is damaged,a number of
mechanisms are activated promptly to limit
bleeding, involving
1-Endothelial cells.
2-Plasma coagulation factors.
3-Platelets.
4-Fibrinolytic system.

HEMOASTASIS-2
These activities are finely balanced between
keeping the blood fluid and preventing
intravascular thrombosis.
1-Pimary hemostasis: immediate but temporary
response to vessel injury . Platelets and von
willebrand interact to form a primary plug , after
which platelet activation occurs and blood
vessels constrict, limiting flow.
2-Secondary hemostasis: (coagulation) :is slower
process that results in the formation of a fibrin
clot .

Coagulation is initiated when vascular
damage exposes extravascular tissue
factor initiating activation of factor V11,
factor X and prothrombin with subsequent
activation of factor V,V111,1X,X1,and
X111,leading to accelerated and sustained
generation of fibrinogen to fibrin and
formation of durable clot.
3-Fibrinolysis: activation of fibrin-bound
plasminogen resulting in clot lysis.
ROLE OF ENDOTHELIAL
CELLS IN HEMOSTASIS
Blood vessels are lined with endothelial
cells,which synthesize and secrete various
agents,that regulate hemostasis.
1-Procoagulant(prothrombotic) agents:
tissue factor, von Willebrand factor, F V ,F
VIII.
2-Anticoagulant(antithrombotic) agents:
prostacyclin,Nitric oxide,endothelin-1.

ROLE OF PLATELETS IN
HEMOSTASIS
1.
2.
3.
4.
5.
Each megacaryocyte produces 10002000 platelets,which
remain in the circulation for about 10
days.
Releasing of hemostatic proteins.
Platelet adhesion.
Platelet aggregation.
COAGULATION SYSTEM
Coagulation factors: are plasma proteins
synthesized in the liver which ,when activated
lead to the deposition of fibrin.
1-Initiation phase: leads to the formation of the
complex TF-VIIa.
2-Amplification phase: leads to the formation of a
small amount of thrombin from prothrombin.
3-Propagation phase: leads to the formation of
much larger amounts of fibrin.

INHIBITORS OF
COAGULATION
Are proteins that inhibit activated procaogulation
enzymes and prevent excessive intravascular
coagulation
Raised levels are not associated with bleeding.
Reduced levels may predispose to thrombosis.
Antithrombin.
Protein C, Protein S.
Tissue Factor Pathway Inhibitor (TFPI).
FIBRINOLYSIS

Small amouns of fibrin are constantly
deposited within the vascular system and
are removed by the fibrinolytic system
Plasminogen
Plasmin
Fibrin
FDPs
ASSESSMENT OF BLEEDING
SYMPTOMS
1-Careful and full clinical history and
examination.
(determining whether a bleeding is present
or likely congenital or acquired, mild or
severe and involving primary or secondary
hemostasis )
2-Appropriate lab. investigations.
3-Other investigations.
HISTORY
1.
2.
3.
4.
5.
6.
7.
1-Site of bleeding( dental extractions,
circumcision, menstration, labor or delivery
and trauma or surgery. Or easy bruising
2-Duration of bleeding and severity.
3-Precipitating cause.
4-Surgery.
5-Family history.
6-Systemic illnesses (acquired bleeding
disorders).
7-Drugs.
Clinical Features of Bleeding
Disorders
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
LABORATORY STUDIES
Initial studies should include a platelet count,

prothrombin time (Pt ), activated partial
thromboplastic time (aPtt) and peripheral
blood smear review.
1.
platelet count low : manual slide review to
rule out a platelet clumping artifact.
2.
Bleeding time (BT) : may detect quantitative or
qualitative disorder of platelets or vWF or
abnormalities of capillary integrity.
prolonged after medication as aspirin.

In vitro platelet aggregation

Von Willebrand factor antigen

von Willebrand factor activity , ristocetin
cofactor (vWF :RCo )
Von Willbrand factor multimer analysis.


Secondary hemostasis
Prothrombin time (Pt) : extrinsic pathway (factor V11,and common
pathway factor X,V ,prothrombin ) coagulation factors and
fibrinogen.
INR : (patient PT/ mean normal PT)ISI 
Activated partial thromboplastin times (aPTT): intrinsic pathway 
(kininogen, prekallikrein, factor X11, factor 1X,factor X1 and factor
V111) and common pathway (factor V,facter X ,prothrombin and
fibrinogen.
Thrombin time (TT) 
Fibrinogin 
Clot urea stability 
Mixing studies coagulation plasma activity .



Coagulation factor disorders
1.
Inherited bleeding
disorders
1.
2.
3.
Hemophilia A and B
Von Willebrand
disease
Other factor
deficiencies

Acquired bleeding
disorders
1.
2.
3.
Liver disease
Vitamin K
deficiency/warfarin
overdose
DIC
Hemophilia A and B
Coagulation factor deficiency
Inheritance
Incidence
Severity
Hemophilia A
Hemophilia B
Factor VIII
Factor IX
X-linked
recessive
X-linked
recessive
1/10,000 males
1/50,000 males
Related to factor level
<1% - Severe - spontaneous bleeding
1-5% - Moderate - bleeding with mild
injury
5-25% - Mild - bleeding with surgery or
trauma
Complications
Soft tissue bleeding
Hemophilia
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
Hemarthrosis (acute)
Treatment of hemophilia A

Intermediate purity plasma products



High purity (monoclonal) plasma
products



Virucidally treated
No functional von Willebrand factor
Recombinant factor VIII


Virucidally treated
May contain von Willebrand factor
Virus free/No apparent risk
No functional von Willebrand factor
Dosing guidelines for hemophilia
A


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
Tranexemic acid or DDAVP (for mild disease only)
Complications of therapy

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
RITUXIMAB AND ACQUIRED HEMOPHILIA(F
VIII INHIBITORS)
STUDY
# OF PATS
Stasi R,Bld
10
103:4424,2004 acquired,titer
4-96BU
Mazj S,Bld
4 acquired
102,03,abs295
5
Wiestner A,Bld 4(3 acquired,1
100,02,3426
hemophilia)
OUTCOME
80% CR
FW 28.5m
100% CR
100% CR
FW 7-12m
Treatment of hemophilia B

Agent



High purity factor IX
Recombinant human factor IX
Dose


Initial dose: 100U/kg
Subsequent: 50U/kg every 24 hours
von Willebrand Disease: Clinical
Features

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
Laboratory evaluation of
von Willebrand disease


Classification
 Type 1
 Type 2
 Type 3
Partial quantitative deficiency
Qualitative deficiency
Total quantitative deficiency
Diagnostic tests:
vonWillebrand type
2
Assay
3
1
vWF antigen

vWF activity

Multimer analysis
Absent

Normal


Normal
Normal
VWF Multimers
plt
NP
1
2A
2A
2B
Proteolysis
3
Treatment of von Willebrand Disease

Cryoprecipitate



DDAVP (deamino-8-arginine vasopressin)





Source of fibrinogen, factor VIII and VWF
Only plasma fraction that consistently contains VWF
multimers
 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
Pathogenesis of DIC
Release of
thromboplastic
material into
circulation
Coagulation
Fibrinolysis
Fibrinogen
Plasmin
Thrombin
Fibrin
Monomers
Fibrin
Clot
(intravascular)
Consumption of
coagulation factors;
presence of FDPs
 aPTT
 PT
 TT
 Fibrinogen
Presence of plasmin
 FDP
Fibrin(ogen)
Degradation
Products
Plasmin
Intravascular clot
 Platelets
Schistocytes
Disseminated Intravascular Coagulation
(DIC)
Mechanism
Systemic activation
of coagulation
Intravascular
deposition of fibrin
Thrombosis of small
and midsize vessels
with organ failure
Depletion of platelets
and coagulation factors
Bleeding
Common clinical conditions associated
with
Disseminated Intravascular Coagulation
Activation of both coagulation and fibrinolysis
Triggered by

Sepsis

Trauma



Head injury
Fat embolism
Malignancy

Obstetrical
complications


Amniotic fluid embolism
Abruptio placentae

Vascular disorders

Reaction to toxin (e.g.
snake venom, drugs)

Immunologic disorders


Severe allergic reaction
Transplant rejection
Disseminated Intravascular
Coagulation
Treatment approaches

Treatment of underlying disorder

Anticoagulation with heparin

Platelet transfusion

Fresh frozen plasma

Coagulation inhibitor concentrate (ATIII)
Classification of platelet
disorders

Quantitative
disorders




Abnormal distribution
Dilution effect
Decreased
production
Increased
destruction

Qualitative disorders


Inherited disorders
(rare)
Acquired disorders



Medications
Chronic renal failure
Cardiopulmonary
bypass
Platelet interaction
Thrombocytopenia
Immune-mediated
Idioapthic
Drug-induced
Collagen vascular disease
Lymphoproliferative disease
Sarcoidosis
Non-immune mediated
DIC
Microangiopathic hemolytic anemia
Incidence of adult ITP increases with
age
Incidence (per 105 / year)
Age (yrs)
Female
Male
Total
15-39
40-59
60+
2.3
3.2
4.6
1.3
1.1
4.4
3.6
4.3
9.0
Total
3.2
2.0
2.6
Frederiksen and Schmidt, Blood 1999:94;909
Initial Treatment of ITP
Platelet count
(per µl)
Symptoms
>50,000
None
20-50,000
Not bleeding
Bleeding
Treatment
None
Steroids
IVIG
<20,000
Not bleeding
Steroids
Bleeding
IVIG
Hospitalization
Liver Disease and Hemostasis
1.
Decreased synthesis of II, VII, IX, X, XI, and
fibrinogen
2.
Dietary Vitamin K deficiency (Inadequate
intake or malabsortion)
3.
Dysfibrinogenemia
4.
Enhanced fibrinolysis (Decreased alpha-2antiplasmin)
5.
DIC
6.
Thrombocytoepnia due to hypersplenism
Management of Hemostatic Defects
in Liver Disease
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
Laboratory Evaluation of Bleeding
Overview
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
Coagulation cascade
Intrinsic system (surface contact)
XII
Extrinsic system (tissue damage
XIIa
Tissue factor
XIa
XI
IX
IXa
VIII
VIIa
VIIIa
X
Vitamin K dependant factors
VII
Xa
V
Va
II
Fibrinogen
IIa
(Thrombin)
Fibrin
Laboratory Evaluation of the
Coagulation Pathways
Partial thromboplastin time
(PTT)
Prothrombin time
(PT)
Surface activating agent
(Ellagic acid, kaolin)
Phospholipid
Calcium
Thromboplastin
Tissue factor
Phospholipid
Calcium
Intrinsic pathway
Extrinsic pathway
Thrombin time Common pathway
Thrombin
Fibrin clot
Initial Evaluation of a Bleeding
Patient - 1
Normal PT
Normal PTT
Abnormal
Urea
solubility
Factor XIII
deficiency
Normal
Consider evaluating for:
Mild factor deficiency
gammopathy
Abnormal fibrinolysis
(a2 anti-plasmin def)
Monoclonal
Platelet disorder
Vascular disorder
Initial Evaluation of a Bleeding
Patient - 2
Normal PT
Abnormal PTT
Repeat
with
50:50
mix
50:50 mix is
abnormal
Test for inhibitor activity:
Specific factors: VIII,IX, XI
Non-specific (anti-phospholipid
Ab)
50:50 mix is
normal
Test for factor deficiency:
Isolated deficiency in intrinsic pathway (factors VIII,
IX, XI)
Multiple factor deficiencies (rare)
Initial Evaluation of a Bleeding Patient 3
Abnormal PT
Normal PTT
Repeat
with
50:50
mix
50:50 mix is
abnormal
Test for inhibitor activity:
Specific: Factor VII (rare)
Non-specific: Anti-phospholipid
(rare)
50:50 mix is
normal
Test for factor deficiency:
Isolated deficiency of factor VII (rare)
Multiple factor deficiencies (common)
(Liver disease, vitamin K deficiency, warfarin,
DIC)
Initial Evaluation of a Bleeding Patient 4
Abnormal PT
Abnormal PTT
Repeat
with
50:50
mix
50:50 mix is
abnormal
Test for inhibitor activity:
Specific : Factors V, X, Prothrombin,
fibrinogen (rare)
Non-specific: anti-phospholipid
(common)
50:50 mix is
normal
Test for factor deficiency:
Isolated deficiency in common pathway: Factors V,
X,
Prothrombin, Fibrinogen
Multiple factor deficiencies (common)
(Liver disease, vitamin K deficiency, warfarin,
Coagulation factor deficiencies
Summary
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, prekallikrein, HMWK deficiencies
do not cause bleeding
Thrombin Time

Bypasses 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
Causes of prolonged Thrombin Time






Heparin
Hypofibrinogenemia
Dysfibrinogenemia
Elevated FDPs or paraprotein
Thrombin inhibitors (Hirudin)
Thrombin antibodies
Bleeding time and bleeding

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
Treatment Approaches to
the Bleeding Patient







Red blood cells
Platelet transfusions
Fresh frozen plasma
Cryoprecipitate
Cyclokapron
DDAVP
Recombinant Human factor VIIa
Red blood cell transfusions
Adverse reactions
Immunologic reactions
Hemolysis
Anaphylaxis
Febrile reaction
Urticaria
Non-cardiogenic
pulmonary edema
RBC incompatibility
Usually unknown; rarely against IgA
Antibody to neutrophils
Antibody to donor plasma proteins
Donor antibody to leukocytes
Platelet transfusions

Source



Platelet concentrate (Random donor)
Pheresis platelets (Single donor)
Target level


Bone marrow suppressed patient (>10-20,000/µl)
Bleeding/surgical patient (>50,000/µl)
Platelet transfusions - complications

Transfusion reactions




Higher incidence than in RBC transfusions
Related to length of storage/leukocytes/RBC
mismatch
Bacterial contamination
Platelet transfusion refractoriness


Alloimmune destruction of platelets (HLA
antigens)
Non-immune refractoriness





Microangiopathic hemolytic anemia
Coagulopathy
Splenic sequestration
Fever and infection
Medications (Amphotericin, vancomycin, ATG,
Interferons)
Fresh frozen plasma


Content - plasma (decreased factor V and VIII)
Indications





Dose (225 ml/unit)


Multiple coagulation deficiencies (liver disease, trauma)
DIC
Warfarin reversal
Coagulation deficiency (factor XI or VII)
10-15 ml/kg
Note


Viral screened product
ABO compatible
Cryoprecipitate


Prepared from FFP
Content


Indications




Factor VIII, von Willebrand factor, fibrinogen
Fibrinogen deficiency
Uremia
von Willebrand disease
Dose (1 unit = 1 bag)

1-2 units/10 kg body weight
Hemostatic drugs
Tranexemic acid (Cyclokapron)

Mechanism


Prevent activation plaminogen -> plasmin
Dose
1g iv q6-8hrs

Uses





Primary menorrhagia
Oral bleeding
Bleeding in patients with thrombocytopenia
Blood loss during cardiac surgery
Side effects

Optic atrophy
Hemostatic drugs
Desmopressin (DDAVP)

Mechanism


Dose



0.3µg/kg IV q12 hrs
150mg intranasal q12hrs
Uses



Increased release of VWF from endothelium
Most patients with von Willebrand disease
Mild hemophilia A
Side effects


Facial flushing and headache
Water retention and hyponatremia
Recombinant human factor VIIa (rhVIIa;
Novoseven)

Mechanism


Use

Factor VIII inhibitors
Bleeding with other clotting disorders
Warfarin overdose with bleeding

CNS bleeding with or without warfarin

Dose
100 µg/kg IV q 2 hrX2
“Adjust as clinically indicated”





Direct activation of common pathway
Cost (70 kg person) - JD0.66per µg

4,800/dose
Approach to bleeding disorders
Summary

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
THANK
YOU 