You are on page 1of 24

Acquired bleeding disorders

Eusni Rahayu Mohd. Tohit

• The information in this presentation is as per
learning outcomes outlined in course
objectives of programme offered in Universiti
Putra Malaysia.
• Audiences are encouraged to do further
reading based on the reference source
• Inherited • Inherited-Haemophilia,
• Acquired von Willebrand disease
• Acquired-Liver disease,
Mucocutaneous vitamin K deficiency,
bleeding intravascular coagulation
manifestation- (DIC)
purpura, petechia
Vascular Coagulation
disorder disorder Deep bleeding
haematuria, intracerebral

• Arterial-ischemia, • Thrombocytopenia
infraction, gangrene • Platelet dysfunction
• Venous-unilateral leg
Mucocutaneous bleeding
purpura, petechia
Causes of bleeding disorder
• Abnormal bleeding can result from:
– Vascular disorder
– Defective platelet function
– Thrombocytopenia
– Defective coagulation
• Pattern of bleeding is relatively predictable
depending on the etiology
Coagulation disorders

• Can be divided into 2 types:

– Inherited- Hemophilia A, Hemophilia B, von
Willebrand disease
– Acquired-more common than inherited disorder,
usually involved multiple clotting factor
Causes of acquired coagulation disorder
Deficiency of vitamin K Liver disease- Disseminated Inhibitors of Miscellaneous
dependent factors intravascular coagulation
( DIC)

Hemorrhagic disease of Alcohol Infections Specific inhibitors Disease with monoclonal

the newborn (HDN) Factor VIII inhibitor protein
Biliary obstruction Virus: hepatitis Malignancy Non specific L-asparaginase
inhibitors e/g Ab Therapy with heparin,
found in SLE,APLS defibrinating agents,
thrombolytic therapy

Malabsorption of vitamin K Malignancy : Hypersensitivity Massive transfusion

e/g: sprue, gluten induced primary/secondary reactions syndrome

Vitamin K antagonist Generalised tissue

therapy e/g Coumarins damage

4/26/2019 7
Facts :Vitamin K-fat soluble, found in green
vegetables & bacterial synthesis from the gut. Vitamin K deficiency states
Haemorrhagic disease of Biliary /small bowel disease Vitamin K antagonist
the newborn (Warfarin/Coumarin)

Factors leading Liver cell immaturity, reduced synthesis of factors, Decreased in functional
to vitamin K breast fed infants, low reduced absorption of vitamin activity of FII,VII,IX and X
deficiency level of factors, lack of K Interferes with vitamin K
gut bacteria epoxide reductase
Clinical Usually-hemorrhage D2- Depending on site of disease: Use as therapeutic to reduce
features D4 of life Bleeding, jaundice, diarrhoea clot formation in thrombotic
Occasionally-first 2 disease
months In overdose, bleeding may
Lab PT,APTT prolonged. Prolonged PT/APTT with low Prolonged PT/APTT, reduced
investigation Normal platelet count factor levels II,VII,IX,X functional level of II,VII,IX,X
and fibrinogen level. and protein C/S
Monitoring via INR
Treatment • Prophylactic vitamin Prophylaxis vitamin K In overwarfarinisation
K injection Bleeding/invasive procedure : (overdose),vitamin K +/- FFP
• Bleeding- IM vitamin IV vitamin K +/- prothrombin /prothrombin complex
K, if severe give complex concentrate concentrate is given
prothrombin complex
Action of vitamin K in synthesis of vitamin
K dependent factors-FII,VII,IX,X

Adapted from Essential Haematology,AV Hoffbrand PAH Moss, 6th edition

Fact : Liver is the organ where most
clotting factors are synthesized Liver disease
• Multiple hemostatic abnormalities may occur &
contribute to bleeding/thrombotic tendency:
– Decreased synthesis of coagulation factors: II, VII,IX, X, V,
– Increased amount of plasminogen activator
– Functional abnormality of fibrinogen (dysfibrinogenaemia)
– Decreased thrombopoietin production: thrombocytopenia
– Thrombocytopenia-due to hypersplenism
• Release thromboplastin and reduced anti thrombin, protein C and
anti plasmin.
• Impaired removal of activated clotting factors and increased
fibrinolytic activity
Liver disease
Decreased clotting factors
Increased fibrinolytic activity
Dysfunctional fibrinogen

Adapted from

Disseminated intravascular
coagulation (DIC)
• Generalised intravascular deposition of
fibrin with consumption of coagulation
factors and platelets.
• Consequence of widespread endothelial
damage or widespread release of
procoagulant material into the circulation
or widespread platelet aggregation.

4/26/2019 12
Pathogenesis of DIC

Adapted from

Clinical conditions may be associated with DIC
Sepsis Trauma Organ Malignancy Obstetric Vascular Severe Severe
Severe destruction calamities abnormalities hepatic toxic/immunol
infection failure ogical
Gram polytraum severe Solid tumours- amniotic Kasabach snake bites
negative a pancreatitis Adenocarcino fluid Merrit
Meningococc ma (mucin ) embolism syndrome,

Clostridium fat hematological abruptio vascular recreational

welchii embolism malignancy- placentae aneurysm drugs
P Falciparum neurotrau transfusion
ma, reactions

Viral- transplant
varicella, rejections

4/26/2019 14
How to identify patients with DIC ?
• Clinical syndrome, identifying clinical features
• Acute DIC
– Dominated by bleeding-venepuncture sites/wounds,
gastrointestinal tract, oropharynx ,lung, urogenital ,vagina
– Microthrombi-skin lesions, gangrene of extremities,
cerebral ischemia.
• Chronic DIC
– Dominated by thrombosis-arteries, veins &
microcirculation, rarely bleeding
– Usually related to malignancy
Laboratory features
• Platelets & red cells • Fibrinolysis function
– FBC-thrombocytopenia – Low fibrinogen level
– FBP-anisocytosis, – Increased D-Dimer
* Coagulation function
– Prolonged PT, APTT, TT

Adapted from

What is the role of laboratory tests?
To support the diagnosis of DIC and monitor progress.
• Prolonged prothrombin • Raised fibrinogen
time(PT) and activated degradation product –
partial thromboplastin increased lysis by plasmin
time (APTT)-consumption
of coagulation factors • Raised D-dimer (fibrin
degradation product)-
• Prolonged thrombin time increased lysis by plasmin.
(TT)-low levels of
fibrinogen & high • FBP-features of
fibrinogen degradation microangipathic hemolytic
products (FDPs) anaemia: schistocytes,
• Reduced platelet count - spherocytes,thrombocyto
consumption of platelet
penia (intravascular fibrin) 17
What to do in cases of DIC?
• Consequences of a clinical cause
• Keystone to treatment : specific & forceful treatment of
underlying cause.
• Resuscitation of circulatory support-maintain blood
pressure and respiratory system.
• Supportive treatment in the form of blood component
– Fresh frozen plasma, packed red cells, platelet
concentrates and cryoprecipitate may be used
• Other promising therapy- anti thrombin, recombinant
activated protein C concentrates, heparin.
Why those blood components are chosen?
• Packed red cells-patients bleed extensively and
red cells given to help carry oxygen to various
organ to prevent hypoxic damage.
• Fresh frozen plasma-rich in clotting factors, thus
to replace the depletion of clotting factors.
• Cryoprecipitate-rich in fibrinogen.
• Platelet concentrates-replace platelet
consumption ( not based on lab results alone)
What happen if DIC is not corrected?
• Multiorgan failure ensues involving:
– Renal-insufficiency due to thrombosis in microcirculation.
– Lung-adult respiratory distress syndrome
– Cerebral dysfunction-ischemia to the organ.
– Gastrointestinal- hemorrhage
– Liver insufficiency- depletion in clotting factors, more toxic
material generated.
Inhibitors to coagulation factors
Alloantibodies to factor Autoantibodies to factor Antiphospholipid
VIII/IX VIII(usually) antibody
Haemophilia with Acquired haemophilia Antiphospholipid
inhibitor syndrome

Incidence/disease 5-10% of haemophiliac Elderly, associated with Woman, idiopathic,

associated malignancy/post associated with
partum, RA SLE/autoimmune
Clinical features Bleeding, no response Severe bleeding Thrombosis,
to factor infusion recurrent pregnancy
Laboratory test Prolonged APTT, low Prolonged APTT, low Prolonged APTT,
factor assay, presence factor assay, presence
of inhibitor (simple of inhibitor (complex
kinetic) in Bethesda kinetic)in Bethesda unit
Mixing study Not corrected: after 2 hours Not corrected :
immediate & after 2
Management Immunosuppression, factor replacement- LMWH
recombinant, FEIBA, FVIIa
Massive transfusion
• Normal blood volume: 3-5 L
• Massive transfusion: replacement of 1/> blood
volume within 24-hour period.
• Stored blood: depleted in platelet and clotting
• Management:
– Platelet concentrates: maintain >50 X 10^9/L
– Fresh frozen plasma (FFP):PT/aPTT must be maintain
<1.5 times of N
– Cryoprecipitate: to keep fibrinogen >1g/L
– Recombinant VIIa
Haemostasis tests: results in acquired bleeding disorder

Adapted from Essential Haematology,AV Hoffbrand PAH Moss, 6th edition

Learning resources
• Essential hematologyAV Hoffbrand,PAH Mss,JE
Pettit latest edition.
• Illustrated colour text of Hematology,MR
Howard,PJ Hamilton,2nd edition.
• Dacie & Lewis Practical Hematology, latest
edition,SM lewis, BJ Bain, I Bates.