Transcript NABYTE SKAZY OSOCZOWE - Katedra i Klinika Hematologii

ACQUIRED
COAGULATION
ABNORMALITIES
1.
Vitamin K deficiency
2. Liver disease
ACQUIRED
COAGULATION
ABNORMALITIES
- causes
3. Clotting factor inhibitors:
circulating anticoagulants
complications of anticoagulant therapy
4. Incraesed consumption or loss of the
clotting factors:
a) disseminated intravascular coagulation ( DIC)
b) fibrinogenolysis (primary fibrinolysis)
Coagulation abnormalities of vitamin K deficiency
• vitamin K is essential for the final postribosomal
carboxylation of F II, VII, IX, X and the physiologic
anticoagulants, protein C and protein S
Laboratory features:
•
 PT (prothrombin time) and  F II, VII, IX, X
• aPTT (activated partial thromboplastin time) may be
prolonged in severe, protracted vitamin K deficiency
• Levels of PIVKA-II (Proteins induced in vitamin K absence) are
more sensitive than PT
Vitamin K deficiency-etiology
I. Inadequate supply:
1. Dietary deficiency (leafy green vegetables 90-120mcg)
2. Destroying the gut flora by administration of broadspectrum antibiotics
II. Impaired absorption of vitamin K:
1. Biliary obstruction (gallstone, strictures, tumor)
2. Malabsorption of vitamin K(sprue, celiac disease, ulcerative
colitis)
3. Drugs (cholestyramine)
III. Pharmacologic antagonists of vitamin K (coumarins, warfarin)
Abnormalities of hemostasis and coagulation
in liver diseases (1)
I. Decreased synthesis of coagulation factors
1. Fibrinogen, protrombin, clotting F V, VII, IX, X, XI, XII, XIII,
prekallikrein, high molecular weight kininogen
2. Antiplasmins, antithrombin, protein C and protein S
II. Aberrant biosynthesis
1. Of abnormal fibrinogenu
2. Of abnormal analogues of prothrombin, F VII, IX, X
Abnormalities of hemostasis and
coagulation in liver diseases (2)
III. Deficient clearance
1. Of fibrin monomers, fibrinogen degradation products
(FDP)
2. Of activated coagulation factors (IXa, Xa, Xia)
3. Of plasminogen acivators
IV. Accelerated destruction of coagulation factors
1. Intravascular coagulation
2. Localized coagulation (hepatic cell necrosis)
3. Abnormal fibrinolysis
V. Thrombocytopenia and platelet dysfunction (splenomegaly)
Treatment
• Vitamin K doses 10mg
• FFP (invasive procedure)
• Prothrombin complex concentrates
• Platelet transfusion
• Antifibrynolytic agents (dental extraction)
Circulating anticoagulants
Clotting factor inhibitors are
autoantibodies (usually IgG) or
alloantibodies (in hemophilia A)
that inactivate coagulation factors
- Laboratory test: prolonged aPTT
Circulating anticoagulants
I. Antibodies to factor VIII (prolonged aPTT, normal INR)
1. In hemophilia A
2. Postpartum -several months after parturition in asociation with a first pregnancy
3. Various immunologic disorders (rheumatoid arthritis, SLE, penicillin allergy)
4. Older patients without underlying disease
II. Other spontaneous inhibitors (rarely)- against factors: V, IX, XIII, fibrinogen,
III. Lupus anticoagulant (in 30% SLE, rheumatoid arthritis, HIV infection, in
lymphoproliferative disorders, after drugs hydralazine, quinidine, penicillin)
Acquired hemophilia A
• Common bleeding sites are
soft tissue, skin, and mucous membrane
• Treatment – Factor VIII bypassing agents:
- Recombinant activated factor VII
- Plasma-derived factor eight-inhibitor bypassing agent
(FEIBA, also called activated prothrombine complex concentrate)
- To eradicate the inhibitor is recommended
DIC
Disseminated intravascular coagulation
• is an acquired syndrome characterized by
systemic intravascular activation of coagulation,
leading to fibrin deposition in the microvasculature
and small-vessels, contributing to organ dysfunction
• consumption of platelets and coagulation factors
lead to thrombocytopenia and impaired coagulation
and may result in bleeding complications
Clinical conditions that may be complicated by DIC
• Sepsis/severe
infection
• Severe alergic/toxic
reaction
• Trauma
• Obstetrical
conditions
• Malignancy
• Acute leukemias
• Amniotic fluid
embolism
• Kasabach-Merritt
syndrome
• Abruptio placentae
• Vascular
abnormalities
• Solid tumors
• HELLP syndrome
ACUTE DIC-CLINICAL PRESENTATION
• symptoms of underlying disease
• symptom of local thrombosis
• hemorrhagic diathesis
• shock
Diffuse intravascular
coagulation
Microthrombosis
secondary fibrinolysis
FDP
Ischemic tissue damage
anemia
Microangiopathic
tendency
↓ platelets
clotting factors
Bleeding
Acute DIC - laboratory features:
•  Increased D-Dimer level
•  FDP level
•  AT level
•  platelet level
• Bload smear - schistocytes
•  fibrinogen level
•  TT (Thrombin time)
•  aPTT
•  PT (Prothrombin time)
Acute DIC diagnosis
• The basis of the diagnosis is the knowledge of
the underlying diseases
• Patients suffering from acute DIC need urgent
therapy
• DIC should always be taken into consideration
if a complex coagulation defect in combination
with a underlying disease is observed
Diagnostic algorithm for the
diagnosis of overt DIC (1)
• Risk assessment:
• Does the patient have an underlying
disorder known to be associated
with overt DIC?
• If yes, proceed
Diagnostic algorithm for the
diagnosis of overt DIC (2)
-
Order global coagulation tests
•Platelet count
(>100=0, <100=1, <50=2)
•Elevated fibrin-related markers
(FDP no increase:0, moderate increase:2, strong increase:3)
•Prolonged PT
(<3sec.= 0, >3 but <6 = 1, >6sec. = 2)
•Fibrinogen level (>1g/L=0, <1g/L=1)
If ≥ 5: compatible with overt DIC
CHRONIC (compensated) DIC
In chronic DIC, the activation of the
hemostatic system is minimal since
negative feedback mechanisms as well as
inhibitors can limit the activation process so
that microthrombi do not occur and
bleeding episodes are rare phenomena
Chronic DIC - etiology
1. Obstetric complications: eclampsia, the death fetus syndrom
2. Vascular disorders:
giant hemangiomas (Kasabach Merrit syndrome), Leriche
syndrome, Raynaud,s disease
3. Carcinomas
4. Hematology disorders: myelofibrosis, polycythemia vera, PNH
5. Reumathoid disorders: SLE, sclerodermia
6. Kidneys disorders: glomerulonephritis, HUS
7. Another: vasculitis allergica, diabetes mellitus
PRIMARY FIBRINOLYSIS (FIBRINOGENOLYSIS)
DEFINITION:
primary fibrinolysis occurs when plasmin is
generated in the absence of DIC
◊ This has been described in hepatic disorders, prostatic
carcinomas, and cases without apparent cause
◊ At present, most cases of primary fibrynolysis are
iathrogenically induced during thrombolytic therapy
Plasminogen
intrinsic
activation
factor XIa, XIIa, kallikrein
kininogen
extrinsic
activation
tPA, uPA
exogenous
activation
streptokinase
or APSAC
Plasmin
Fibrinogen
FDP
Fibrin
FDP + D-Dimer
Acquired coagulation abnormalities - diagnostics
I
History
II
Physical examination
III Laboratory features
- morphology
- blood smear
- bleeding time
- prothrombin time (PT), INR
- aPTT
- thrombin time (TT)
- fibrinogen
- fibrin(ogen) degradation products (FDP)
- D-dimer
- antithrombin
Diferentiation of aquired coagulation abnormalities
PT
aPTT Platelet Fibrinogen
TT
FDP
D-Dimer
AT




N




N
N
N
N
N
N
N

N
N
N
count
Acute DIC



Chronic DIC
N 
N
N

N
Fibrinogenolysis
N
Heparin overdosage


Dicumarol

N
overdosage or
prothrombin complex
factors defficiency
N
N

N

N
N
ACA – DIC THERAPY
1. Treatment of the underlying disorder
2. Treatment of shock
3. Replacement therapy
- platelet concentrates
- RBC
- FFP
- Cryoprecipitate (fibrinogen)
- Activated protein C (drotrecogin alfa)
4.
Heparin treatment
unfractioned heparin or low-molecular weight heparin
acrocyanoza, purpura fulminans, dermal necrosis, venous thromboembolism
Treatment – thrombosis predominantes
• Continous infusion of UFH
• Prophilactic doses of heparin or LMWH
• Especially, severe purpura fulminans,
acral ischemia, vascular skin infarction
Treatment - bleedings
• Transfusion of platelets or plasma (components)
including FFP and/or prothrombin complex
concentrate (fluid overload)
• Severe hipofibrynogeneamia (<1g/L):
FFP, fibrionogen concentrate and cryopercipitate
CASE PRESENTATION