Disorders under coagulopathy as a part of bleeding disorder

1. COAGULOPATHY
Dr. Md Ishtiaqul Haque Mortuza
Resident (Phase-A)
Urology, BSMMU

2. Contents
• Hemostasis
• Coagulation Process
• Definition of Bleeding disorders
• Definition & Extent of Coagulopathy
• Medical Conditions under Coagulopathy with their
Management
• Pre operative preparation for the patients with
coagulopathy

3. Hemostasis
• It is the process to maintain the blood in a clot free
state, as well as formation of blood clot at the site of
vascular injury to arrest or limit the extent of
bleeding

4. Factors responsible for hemostasis
• Vascular Endothelium
• Platelet
• Clotting factor & coagulation cascade
• Fibrinolytic system (for counter regulation)

5. Role of Vascular Endothelium
Anti coagulant effect Procoagulant effect

6. Process of Coagulation
1. Transient vasoconstriction
2. Primary hemostasis
3. Secondary hemostasis
4. Clot stabilization & resorption

7. Fig: Mechanism of hemostasis after vascular injury

8. Fig: Mechanism of hemostasis after vascular injury

9. Clotting factors
I- Fibrinogen
II- Prothrombin
III- Tissue factor/tissue
thromboplastin
IV- Ionized Calcium
V- Proaccelerin
VII- Pro convertin
VIII- Anti hemophilic factor
IX- Christmas factor
X- Stuart-Prower factor
XI- Plasma thromboplastin
antecedent
XII- Hageman factor
XIII- Fibrin stabilizing factor
vWF- Von willibrands factor
Pre kallikrein
HMWK- high molecular wt
of kininogen

11. Role of Platelet Phospholipid &
Calcium in Coagulation process

12. • Bleeding Time (BT):
– time for the formation of platelet plug
• Clotting Time (CT):
– time for the formation of fibrin polymer
(intrinsic + common pathway)
• Prothrombin Time (PT):
– time for the formation of prothrombin to thrombin
(Extrinsic + common pathway)
• Activated Partial Thromboplastin Time (APTT):
– time for the formation of fibrin monomer
(intrinsic + common pathway)

13. Fibrinolytic System

14. What is bleeding disorder?
• Disorders associated
with abnormal bleeding
due to platelet defect,
clotting factor defect or
vessel wall defect
Bleeding disorder
Clotting
factor
defect
platelet
defect
vessel wall
defect

15. Definition of Coagulopathy
Group of medical disorders where derangement of
hemostasis occur due to any of the following
condition:
• Deficiency/inadequate function of platelet, or
• deficiency of clotting factor or
• excessive activity of fibrinolytic system
Ref: de gruchy 5th

16. Vascular
defect
(Non
thrombocyto-
penic purpura)
Platelet defect
Clotting factor
defect
Coagulopathy Purpuric disorderTrauma
Extent of Coagulopathy

17. Medical Conditions under Coagulopathy
• Disorders due to Platelet defect
• Disorders due to Coagulation defect
• Trauma induced coagulopathy (TIC)

18. Quantitative (Thrombocytopenia)
• Primary
– Immune/Idiopathic
Thrombocytopenic purpura
• Secondary
– ↓ Bone marrow production
– ↑ Platelet Destruction
– ↑ Platelet Cosumption
Qualitative (Thrombasthenia)
• Congenital
– Glanzmann’s thrombasthenia
– Burnard souliar syndrom
– Secondary to Von willibrand’s
disease
• Acquired
– Myeloproliferative disorders
– Uremia
– Drugs (e.g. NSAID, Aspirin)
– Autoantibodies
– Fibrin degradation products
Disorders due to platelet defect

19. Disorders of coagulation defect
Congenital Causes
• Hemophilia A
• Hemophilia B
• Von willebrands Disease
• Other specific factor
deficiency
Acquired Causes
• Liver disease
• DIC
• Vitamin K deficiency
• Massive blood transfusion
• Anticoagulant drugs
•Coagulation defect Can be due to single factor deficiency or Multiple factor deficiency

20. We will focus on following conditions
Platelet defect
• ITP
• Secondary
Thrombocytopenia
Coagulation defect
• Hemophilia
• Von Willebrands
Diseases
Both Platelet &
coagulation defect
• DIC
• TIC

21. Primary Thrombocytopenia(ITP)
• Antiplatelet auto-antibody(IgG) is formed against
membrane glycoprotein IIb-IIIa
• This Antigen-Antibody complex dose not causes direct
lysis of platelet by activating complement system
• Rather it causes premature removal of platelets by
Mononeuclear phagocyte system
• Most common in children and young adults
• Females are more affected (2:1 female:male ratio)

22. • In children often precipitated
by viral infection
• Muco-Cutaneous bleeding
o Petechi,Pupura,Echymoses
o Epistaxis
o Gum bleeding
o GIT Bleeding
• Bleeding from internal organ
may occur
• Often self limiting
1. Platelet count < 10,000/ml
2. BT > 30 minutes or longer
3. CT normal
4. Tourniquet test positive in
most cases
5. PBF:
• abnormal platelet may be
found
6. Bone marrow:
• megakaryocytes & their
precursor are normal
7. Anti-platelet Ab(IgG) may be
demostrated
Clinical features Lab findings
Clinical and Lab findings

23. Treatment
• Treatment
1. Prednisolon 1-2 mg/kg/day
2. IV Immunoglobulin 1gm/kg/day for 2-3 days
3. Danazole 600mg/day (response rate is 50%)
4. Immunosuppressive drugs (e.g. Vincristine,
Vinblastin,Azathioprine,Cyclophosphamide)
5. Splenectomy (for steroid non responders)
• Prognosis
– Good if disease is initially controlled with prednisolone
– Splenectomy is definite Rx

24. Secondary Thrombocytopenia
Etiology
1. Decreased bone marrow production
a. Aplastic anemia
b. Leukemias
c. Lymphoma
d. Multiple Myeloma
e. Secondary Metastesis
f. Infections (Dengue,HIV)
2. Increased platelet destruction
a. Drugs (cytotoxic, sulphonamide, trimethoprime, chloramphenicol,
chloroquine)
b. Hyperspleenism
c. Post transfusion Alloimune thrombocytopeina
3. Increased platelet consumption
a. DIC
b. Septicemia

25. Clinical features
Superficial Bleeding
• Petechi,Pupura,Echymoses
• Epistaxis
• Gum bleeding
• GIT Bleeding
• Bleeding from internal
organ may occur
Lab findings
– Platelet count ↓
– BT ↑↑
– CT normal
– PT normal or ↑
– PBF:
• abnormal platelet may be
found
– Bone marrow:
• megakaryocytes & their
precursor are reduced
Clinical and Lab findings

26. Treatment
• Platelet transfusion
• Treatment of underlying cause

27. Von Willebrand’s Disease
• Autosomal dominant disease
– gene for vWF located in chromosome 12
• vWF is synthesized by
– endothelial cells &
– megakaryocytes.
• It acts as
– Adhesive protein
• bridges collagen to platelet receptor GP1b
– Carrier protein
• for Factor VIII (anti hemophilic factor)

28. How vWF works?

30. Why platelet transfusion is discouraged in
dengue hemorrhagic fever??
Dengue haemorrhagic fever
↓ADAMTS
(vWF cleaving
protease)
↑vWF
multimer
(active form)
↑ platelet
adhesion &
consumption
↑bleeding &
microthromb
us

31. Clinical and Lab findings
Clinical feature
• Mainly superficial bleeding:
– Bruising
– Epistaxis
– Gum bleeding
– Hematemesis,Malena
– Hematuria
– Menirrhagia
• Rarely Deep tissue bleeding
haematoma,haemarthrosis are
only seen in patients with marked
concomitant factor VIII deficit.
Lab findings
• Platelet count Normal
• BT ↑↑
• CT ↑↑
• APTT ↑↑
• Normal PT
• vWF assay : vWF ↓
• vWF Ristocetin cofactor
activity ↓
• Factor VIII assay: Factor VIII ↓

32. Treatment
• For mild to moderate hemorrage
(vWF Ristocetin cofactor 10-40 IU/dl)
Desmopressin (DDAVP: 1-desamino-8d arginine vasopressin)
– Not applicable for Children <3 years old
– Intranasal spray (for home treatment)
• 300 µgm
– For Pre operative prophylaxis
• .3 µgm/kg in 50-100 ml N/S IV over 30-60 minutes
• vWF level usually raised 3 units within 90 minutes
• For Severe haemorrhage
(vWF Ristocetin cofactor <10 IU/dl)
Factor VIII transfusion

33. Haemophilia
• X linked recessive disorder
• Usually Male are affected
• Female are Carrier
• But female can be affected also

34. Types
Hemophilia A
• Deficiency of Factor VIII
(anti hemophilic factor)
Hemophilia B
• Deficiency of Factor IX
(Christmas factor)
II
XII
XI
IX
VIII VII
X
V
I
XIII
Stable clot
According to deficiency of clotting factors
According to severity
Mild : 5%-30% of normal level
Moderate: 1-5% of normal level
Severe: <1% normal level

35. Inheritence

36. Female Sufferer

37. Clinical Features
Female may show symptoms in
• When Carrier mother crosses with hemophilic
father
• Turner syndrom (45 X0)
Deep tissue bleeding (80-90%)
• Hemarthrosis 70-80%
• Hematomas 10-20%
subcutaneous or intramuscular
Superficial bleeding(10-20%)
Muco-cutaneous Bleeding from-
Nasal mucosa,GIT mucosa,Intra-abdominal organs
Heavy bleeding after minor cut injury

38. Lab findings
• Platelet count Normal
• BT normal
• CT ↑↑
• APTT ↑↑
• Normal PT
• Factor VIII/IX assay:
– Factor VIII ↓ in Hemophila A
– Factor IX ↓ in hemophilia B
• Factor VIII/IX inhibitor assay

39. Management of hemophilia
• Treatment for the patient
• Genetic counselling for the parents
– For subsequent pregnancy
– Chorionic villous sampling on 10th week of
gestation for early detection
– Amniocentesis on 16th week of gestation

40. Treatment of Haemophilic patient
• Factor VIII or Factor IX Prophylaxis
– prophylaxis is primary Rx
– therapy is started in patients as young as 1 y and continues into adolescence
– usually requires the administration of FVIII 3 times per week, FIX every 10 days
interval
• Other options:
– Monoclonal Ab(Rituximab)
– Desmopressin (can ↑ fVIII upto 4 fold in mild hemorrhagic episodes only)
– Antifibrinolytics (Tranexamic acid) are useful in acute hemorrhagic episodes
• Rx of Factor VIII or Factor IX inhibitors
– aPCC(activated prothombin complex concentrate)
– Monoclonal Ab(Emicizumab) bridges between FIX & FX
– Activated factor VII
• Rx & rehabilitation for hemophilia synovitis
– Radio-synovectomy (by Yittrium 90 & Rhenium 186) ↓hemarthrosis, ↓joint
damgae, prevent arthropathy
– Arthroplasty

41. Factor VIII maintenance
• Mild hemorrhages (early hemarthrosis, epistaxis, gingival bleeding)
– Maintain an FVIII level of 30%
• Major hemorrhages (hemarthrosis or muscle hematoma with pain,
prophylaxis after head trauma with negative findings on
examination):
– Maintain an FVIII level of 50%
• Life-threatening bleeding episodes (major trauma or surgery,
advanced or recurrent hemarthrosis):
– Maintain an FVIII level of >80 %
– after stabilization, maintain levels above 40-50% for a minimum
of 7-10 days
Factor VIII maintenance
• Mild hemorrhages (early hemarthrosis, epistaxis, gingival bleeding)
– Maintain an FVIII level of 30%
• Major hemorrhages (hemarthrosis or muscle hematoma with pain,
prophylaxis after head trauma with negative findings on
examination):
– Maintain an FVIII level of 50%
• Life-threatening bleeding episodes (major trauma or surgery,
advanced or recurrent hemarthrosis):
– Maintain an FVIII level of >80 %
– after stabilization, maintain levels above 40-50% for a minimum
of 7-10 days

42. Complication
• Complication due to Rx
– Development of Antibodies against clotting factors
– Transmission of Viral Diseases like HBV,HCV,HIV.
• Complication due to haemorrhage
– Synovitis of large joints, Arthropathy
– Muscular atrophy due to hematoma
– Entrapment mononeuropathy due to pressure from
hematoma

43. Hemophilia is a life long disease
• A person born with
haemophilia will have it for
life.
• The level of factor VIII or IX in
his blood usually stays the
same throughout his life.

44. Surgery in a child with Hemophilia
For Minor Surgery
Factor VIII should be >50% than normal predicted
value
For Major Surgery
Factor VIII should be >80% of normal predicted
value
It should be transfused just before surgery and
repeat 12 hours after initial dose to pass the
reactionary phase
Half life is 8-12 hours

45. Calculation
• One unit of Factor VIII or Factor IX:
– the amount of FVIII & FIX in 1 mL of plasma (1 U/mL or 1%)
– FVIII 1 U/kg increases FVIII plasma levels by 2%
– FIX 1 U/kg increases FVIII plasma levels by 2%
• The volume of distribution
– FVIII is that of plasma, approximately 50 mL/kg
– FIX is approximately 100 mL/kg
• Units Factor VIII = (weight in kg) x (50 mL plasma/kg) x
(1 U FVIII/mL plasma) x (desired FVIII level - native FVIII level)
• Units factor IX = (weight in kg) x (100 mL/kg) x
(1 U Factor IX/mL) x (desired factor IX level - native Factor IX level)

46. Disseminated Intravascular Coagulation (DIC)
• It is a Thrombo-hemorrhagic disorder which
apperas as a complication of several
conditions
• There is rapid consumption of platelet &
clotting factors leading to thrombosis
• As well as activation of plasminogen causing
fibrinolysis that leads to bleeding

47. Causes of DIC
• Massive Tissue injury
– Extensive Surgery
– Severe Burn
– Massive trauma/Crush injury
• Others
– Shock
– Heat stroke
– Snake bite
– Acute Intravascular Hemolysis
• Infection
– Gm Negetive
– Meningococcemia
– Pneumococcemia
– Malaria, Histoplasmosis,
Aspergilosis
• Malignancy
– Pancreas, Prostate, stomach,
lungs
• Obstetric complication
– Abruptio placenta
– Septic abortion
– Retained dead fetus
– Pre Eclampsia
– Amniotic fluid embolism

48. Pathophysiology of DIC

49. Clinical features & Lab findings
Clinical Features
• Clinical manifestations
include the manifestations
of underlying causes
• There may be signs of
concealed or revealed
bleeding
• Also signs of systemic
thrombosis may be present
Lab findings
• Platelet count ↓
• BT ↑↑
• CT ↑↑
• PT ↑↑
• APTT ↑↑
• Factor II,V,VII,X - ↓
• FDP/D-dimer- ↑

50. Treatment
• General measure
– Correction of dehydration, acidosis, shock
– Broad-spectrum antibiotics
• Transfusion
– Platelet transfusion (if count <20,000/ml)
– FFP
– Cryoprecipitate (to maintain fibrinogen level
>150mg/dl)
• Treatment of underlying causes

51. Trauma Induced Coagulopathy (TIC)
• Combination of tissue trauma (e.g. Major
surgery) & hypovolemic shock leads to
development of an endogenous coagulopathy
called Acute traumatic coagulopathy(ATC)
• ATC is associated with 4 fold increase in
mortality
• ATC is the component of TIC

52. Pathophysiology of TIC

53. Pathophysiology of TIC
1. trauma → haemorrhage → Shock→ hypoperfusion →anaerobic
glycolysis →Metabolic acidosis → decrease coagulation protease
function→ Further bleeding occurs
2. trauma → haemorrhage → Shock → under perfused muscle/exposed
body cavity → unable to generate heat →hypothermia → poor
coagulation function at low temperature → Further bleeding ensues
3. trauma → ↓ plasminogen activator inhibitor(PAI) →hyper fibrinolysis
→ Further bleeding occurs
4. trauma → haemorrhage →loss of clotting factors due to
bleeding/dilution of clotting factors due to massive infusion or
transfusion → Further bleeding ensues

54. Management of TIC
According to ATLS protocol
1. Primary survey & simultaneous resuscitation
• c= Control of active bleeding
• A= Airway maintenance with cervical spine protection
• B= Breathing by oxygen
• C= Circulation maintenance by blood/fluid
• D= Disability or Neurological status
• E= Exposed adequately in a controlled environment
2. Secondary survey (head to toe examination)
3. Definitive treatment
• Control of bleeding & definite surgery for trauma
• Correction of hypovelemia
• correction acidosis
• Control of hypothermia
• Antibiotics
• Tetanus IG
• Rx of complication

55. Thank you