Beruflich Dokumente
Kultur Dokumente
Dairion Gatot
Divisi Hematologi & Onkologi Medik Bagian Penyakit Dalam
FK USU RSUP H Adam Malik/ RS Pirngadi Medan
Objectives
I.
II.
III.
IV.
V.
Objectives - I
Coagulation
factor disorders
Site of bleeding
Skin
Mucous membranes
(epistaxis, gum,
vaginal, GI tract)
Petechiae
Yes
No
Ecchymoses (bruises)
Small, superficial
Large, deep
Extremely rare
Common
Yes
No
Immediate,
usually mild
Petechiae
(typical of platelet disorders)
Ecchymoses
(typical of coagulation
factor disorders)
Objectives - II
Inherited bleeding
disorders
Hemophilia A and B
vonWillebrands disease
Other factor deficiencies
Acquired bleeding
disorders
Liver disease
Vitamin K
deficiency/warfarin
overdose
DIC
Hemophilia A and B
Coagulation factor deficiency
Inheritance
Incidence
Severity
Complications
Hemophilia A
Hemophilia B
Factor VIII
Factor IX
X-linked
recessive
1/10,000 males
X-linked
recessive
1/50,000 males
Hemophilia
Clinical manifestations (hemophilia A & B are
indistinguishable)
Hemarthrosis (most common)
Fixed joints
Urinary tract
CNS, neck (may be life-threatening)
Hemarthrosis (acute)
Treatment of hemophilia A
Mild bleeding
Major bleeding
Adjunctive therapy
-aminocaproic acid (Amicar) or DDAVP (for mild disease only)
Complications of therapy
Viral infections
Hepatitis B
Hepatitis C
HIV
Human parvovirus
Hepatitis A
Other
Hepatitis serology
Negative
Hepatitis B virus only
Hepatitis C virus only
Hepatitis B and C
Blood 1993:81;412-418
HIV -positive
(n=382)
53%
% positive
HIV-negative
(n=345)
47%
% negative
1
1
24
74
20
1
45
34
Treatment of hemophilia B
Agent
High purity factor IX
Recombinant human factor IX
Dose
Initial dose: 100U/kg
Subsequent: 50U/kg every 24 hours
Incidence - 1/10,000
Laboratory evaluation of
von Willebrand disease
Classification
Type 1
Type 2
Type 3
Diagnostic tests:
Assay
vWF antigen
vWF activity
Multimer analysis
Normal
vonWillebrand type
2
Normal
Normal
Absent
Cryoprecipitate
Vitamin K deficiency
Source of vitamin K
flora
Green vegetables
Synthesized by intestinal
Sepsis
Triggered by
Malignancy
Obstetrical complications
Amniotic fluid embolism
Abruptio placentae
Trauma
Head injury
Fat embolism
Vascular disorders
Reaction to toxin (e.g.
snake venom, drugs)
Immunologic disorders
Severe allergic reaction
Transplant rejection
Intravascular
deposition of fibrin
Thrombosis of small
and midsize vessels
with organ failure
Depletion of platelets
and coagulation factors
Bleeding
Pathogenesis of DIC
Release of
thromboplastic
material into
circulation
Coagulation
Fibrinolysis
Fibrinogen
Plasmin
Thrombin
Fibrin
Monomers
Fibrin
Clot
(intravascular)
Fibrin(ogen)
Degradation
Products
Plasmin
Consumption of
coagulation factors;
presence of FDPs
aPTT
PT
TT
Fibrinogen
Presence of plasmin
FDP
Intravascular clot
Platelets
Schistocytes
Platelet transfusion
Quantitative disorders
Abnormal distribution
Dilution effect
Decreased production
Increased destruction
Qualitative disorders
Inherited disorders
(rare)
Acquired disorders
Medications
Chronic renal failure
Cardiopulmonary bypass
Thrombocytopenia
Immune-mediated
Idioapthic
Drug-induced
Collagen vascular disease
Lymphoproliferative disease
Sarcoidosis
Non-immune mediated
DIC
Microangiopathic hemolytic anemia
Acute ITP
Chronic ITP
Peak age
Female:male
Antecedent infection
Onset of symptoms
Platelet count at presentation
Duration
Spontaneous remission
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
Symptoms
Treatment
>50,000
None
20-50,000
Not bleeding
Bleeding
None
Glucocorticoids
IVIG
<20,000
Not bleeding
Bleeding
Glucocorticoids
Glucocorticoids
IVIG
Hospitalization
No./total
(%)
Complete response
With glucocorticoids
With splenectomy
370/1447
581/885
(26%)
(66%)
78/1761
(4%)
1027/1606
(64%)
134 patients with severe ITP studied for mean of 10.5 yrs
CR and PR patients (85%)
No increased mortality compared to control population
Non-responders/maintenance therapy
Increased morbidity due to ITP-related hospitalizations
Increased mortality related equally to bleeding and infection
Objectives - III
2.
3.
Dysfibrinogenemia
4.
5.
DIC
6.
Management of Hemostatic
Defects in Liver Disease
Treatment
Treatment
Treatment
Guidelines
INR therapeutic-5
Clinical situation
Guidelines
Omit warfarin
Vitamin K 10 mg slow IV infusion
FFP or PCC (depending on urgency)
Repeat vitamin K injections every 12 hrs as needed
Omit warfarin
Vitamin K 10 mg slow IV infusion
PCC ( or recombinant human factor VIIa)
Repeat vitamin K injections every 12 hrs as needed
Local: Single site of bleeding usually rapid with minimal coagulation test
abnormalities
Hemostatic failure: Multiple site or unusual pattern with abnormal coagulation tests
2.
3.
1.
2.
1.
2.
Preexisting abnormality
Special cases (e.g. Cardiopulmonmary bypass)
Review pre-operative testing
Obtain updated testing
Objectives - IV
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
Coagulation cascade
Intrinsic system (surface contact)
XII
XIIa
Tissue factor
XIa
XI
IX
IXa
VIII
VIIa
VIIIa
X
VII
Xa
V
Va
II
Fibrinogen
IIa
(Thrombin)
Fibrin
Prothrombin time
(PT)
Thromboplastin
Tissue factor
Phospholipid
Calcium
Intrinsic pathway
Extrinsic pathway
Thrombin time
Common pathway
Thrombin
Fibrin clot
Pre-analytic errors
Heparin contamination
Wrong label
Slow fill
Underfill
Vigorous shaking
Biological effects
Hct 55 or 15
Lipemia, hyperbilirubinemia,
hemolysis
Laboratory errors
Delay in testing
Prolonged incubation at 37C
Freeze/thaw deterioration
Abnormal
Factor XIII deficiency
Normal
Consider evaluating for:
Mild factor deficiency
Abnormal fibrinolysis
(2 anti-plasmin def)
Elevated FDPs
Monoclonal gammopathy
Platelet disorder
Vascular disorder
50:50 mix is
abnormal
Test for inhibitor activity:
Specific factors: VIII,IX, XI
Non-specific (anti-phospholipid Ab)
50:50 mix is
abnormal
Test for inhibitor activity:
Specific: Factor VII (rare)
Non-specific: Anti-phospholipid (rare)
50:50 mix is
abnormal
Test for inhibitor activity:
Specific : Factors V, X, Prothrombin,
fibrinogen (rare)
Non-specific: anti-phospholipid (common)
Sex-linked recessive
Factors VIII and IX deficiencies cause bleeding
Prolonged PTT; PT normal
Thrombin Time
Procedure:
Add thrombin with patient plasma
Measure time to clot
Variables:
Source and quantity of thrombin
Heparin
Hypofibrinogenemia
Dysfibrinogenemia
Elevated FDPs or paraprotein
Thrombin inhibitors (Hirudin)
Thrombin antibodies
Classification of thrombocytopenia
History
Objectives - V
Treatment Approaches to
the Bleeding Patient
CMV-negative patients
Prevent CMV
transmission
Irradiated RBCs
Prevent GVHD
Leukopoor
Previous non-hemolytic
transfusion reaction
CMV negative patients
Prevents reaction
PNH patients
IgA deficient recipient
Prevents hemolysis
Prevents anaphylaxis
Washed RBC
Prevents transmission
RBC incompatibility
Usually unknown; rarely against IgA
Antibody to neutrophils
Antibody to donor plasma proteins
Donor antibody to leukocytes
Volume overload
Bacterial contamination
Hypocalcemia
Massive transfusion
Transfusion-transmitted disease
Infectious agent
Risk
HIV
Hepatitis C
Hepatitis B
Hepatitis A
HTLV I/II
CMV
Bacteria
Creutzfeld-Jakob disease
Others
~1/500,000
1/600,000
1/500,000
<1/1,000,000
1/640,000
50% donors are sero-positive
1/250 in platelet transfusions
Unknown
Unknown
Platelet transfusions
Source
Target level
Transfusion reactions
Higher incidence than in RBC transfusions
Related to length of storage/leukocytes/RBC mismatch
Bacterial contamination
Note
Viral screened product
ABO compatible
Cryoprecipitate
Indications
Fibrinogen deficiency
Uremia
von Willebrand disease
Hemostatic drugs
Aminocaproic acid (Amicar)
Mechanism
Dose
50mg/kg po or IV q 4 hr
Uses
Primary menorrhagia
Oral bleeding
Bleeding in patients with thrombocytopenia
Blood loss during cardiac surgery
Side effects
GI toxicity
Thrombi formation
Hemostatic drugs
Desmopressin (DDAVP)
Mechanism
Increased release of VWF from endothelium
Dose
0.3g/kg IV q12 hrs
150mg intranasal q12hrs
Uses
Most patients with von Willebrand disease
Mild hemophilia A
Side effects
Facial flushing and headache
Water retention and hyponatremia
Mechanism
Use
Dose
90 g/kg IV q 2 hr
Adjust as clinically indicated
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