Bleeding diathesis refers to a group of hematological diseases that interfere with normal hemostasis and cause a bleeding tendency. There are two main types: hypocoagulability and hypercoagulability. Normal hemostasis involves vasoconstriction, platelet plug formation, and coagulation cascade in response to hemorrhage. Bleeding disorders can be caused by abnormalities in vasculature, platelets, or coagulation factors. Clinical features depend on whether the disorder affects platelets or coagulation factors, and include petechiae, ecchymoses, hemarthrosis, and hematomas. Treatment involves corticosteroids, intravenous immunoglobulin, splenectomy, immunosuppress
2. Bleeding disorders
• Def / a group of hematological diseases
interfer with normal hemostasis
• Types :
- Hypocoagulability
- hypercoagulability
( bleeding tendency) ( thrombosis tendency )
3. Normal hemostasis
In case of hemorrhage , there will be normal
responce to stop the bleeding
1- vasocostriction :
Due to :
A- direct myogenic spasm
B- platelet ( throboxane A2)
C- neuronal
4. 2- platelet pulg
• Mechanism :
When there is an endothelial injury
Platelet aggregation will takes place
When the platelets attatched to each other they
will be activated and platelet pulg will occures
9. •I. Congenital
• Deficiency of coagulation factor VIII (hemophilia A)
• Deficiency of coagulation factor IX (hemophilia B)
• Deficiency of coagulation factor XI (hemophilia C)
• Deficiency of other coagulation factors (I, II, V, VII,
IX, X and XIII)
• Deficiency of XII factor, prekallikrein or kininogen,
protein C and S (without excessive bleeding)
• von Willebrand’s disease (angiohemophilia)
11. Terminology
Purpura is the appearance of red or purple discolorations on
the skin that do not blanch on applying pressure(3–10 mm).
A petechia is a small (1 - 2 mm) red or purple spot on the body.
An ecchymosis is subcutaneous purpura larger than 1
centimeter .
Hemarthrosis is a bleeding into joint spaces.
A hematoma is a localized collection of blood outside the blood
vessels.
12. Clinical Features of Bleeding Disorders
Platelet
disorders
Coagulation
factor disorders
Site of bleeding tissues
Skin
Mucous membranes
(epistaxis, gum,
vaginal, GI tract)
Deep in soft
(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
20. Senile Purpura
Solar purpura or Senile purpura is a skin condition characterized by large, sharply outlined, 1to 5-cm, dark purplish-red ecchymoses appearing on the dorsa of the forearms and less often
the hands.The condition is most common in elderly white persons. It is caused by sun-induced
damage to the connective tissue of the skin.
21. Petechiae in patient
with Rocky Mountain
Spotted Fever
Rocky Mountain spotted fever (RMSF) is a tick-borne disease caused by the
organism Rickettsia rickettsii.
26. PROTHROMBIN TIME
• This measures the clotting time of plasma after the
addition of brain extract containing tissue
thromboplastin.
• This will test the extrinsic clotting pathway involving
factors V, VII, X and Fibrinogen.
• The reference range for prothrombin time depends
on the analytical method used, but is usually around
12-13 seconds
• Prolongation of the Prothrombin Time is seen in,
1)
2)
3)
4)
Liver cell dysfunction
Vitamin K deficiency
Warfarin therapy
Disseminated Intravascular Coagulation (DIC)
27. ACTIVATED PARTIAL THROMBOPLASTIN TIME
• This will test for defects in the extrinsic pathway.
• The clotting factors are Factors, XII, XI, IX, VIII, X, V, II
and I
• The typical reference range is between
30 seconds and 50 s
• Prolongation of APTT is seen in,
Haemophilia A and B (Factors VIII and IX)
Von Willebrandt's Disease (stabilizing factor for factor VII
Other factor deficiencies (XII, XI)
Liver failure
Disseminated Intravscular Coagulation.
ed)
28. THROMBIN TIME
• thrombin added to undiluted plasma
• tests the conversion of fibrinogen -> fibrin
• The reference ranges of the Thrombin Clotting
time is generally <22 seconds,
• prolonged in:
-> heparin
-> DIC
-> hypofibrinogenaemia
-> fibrin degradation products
29. FIBRINOGEN
• normal: 1.5-4.0
• high in: acute phase response
• low in:
-> sepsis
-> DIC
FIBRIN DEGRADATION PRODUCTS (FDPs)
• marker of fibrin and fibrinogen breakdown
• The reference range of FDP levels is less than 10
mcg/mL (conventional units) or less than 10 mg/L
(SI units).
30. APTT 50% NP
• mixing of patients sample with pooled normal plasma – 50:50
mix
• failure to correct after mixing:
• -> lupus anticoagulant
ECHIS TIME
•
•
•
•
•
•
snake venom from Echis multisquamatus added to sample
differentiates liver dysfunction from vitamin deficiency
this activates prothrombin without requiring vitamin K
is normal in vitamin K deficiency or warfarin use
The reference ranges is 10.5 - 15 sec
if prolonged:
-> factor deficiency (liver disease)
31. RETIPLASE TIME
• used to detect deficiency or abnormalities in
fibrinogen
• snake venom that has similar action to thrombin but
is resistant to inhibition by antithrombin III
• interpret with TCT
• if retiplase time normal and TCT prolonged:
-> heparin
-> hirudin
-> direct thrombin inhibitors
32. EUGLOBIN LYSIS TIME
• shortened time:
• -> presence of systemic fibrinolytic pathway
activators
UREA SOLUBILITY TEST
• factor 13 stabilises fibrin
• if deficient 5M urea will dissolve it
34. • Children:
• Children do not usually require treatment, Where
this is necessary on clinical grounds.
• high-dose prednisolone is effective, given for a very
short course.
• Intravenous immunoglobulin (i.v. IgG) should be
reserved for very serious bleeding or urgent surgery.
• Chronic ITP is rare and requires specialist
management.
35. • Adults:
• Patients with platelet counts greater than
30 × 10^9/L require no urgent treatment
unless they are about to undergo a
surgical procedure.
36. • First-line therapy :
• consists of oral corticosteroids 1 mg/kg body weight.
• Approximately 66% will respond to prednisolone but relapse
is common when the dose is reduced.
• Only 33% of patients can expect a long-term response and
long term remission is seen in only 10–20% of patients
following stopping prednisolone.
• Patients who fail to respond to corticosteroids or require high
doses to maintain a safe platelet count should be considered
for splenectomy.
37. • Intravenous immunoglobulin (i.v. IgG) is effective, It
raises platelet count in 75% and in 50% the platelet
count will normalize , Responses are only transient
(3–4 weeks) with little evidence of any lasting effect.
• However, it is very useful where a rapid rise in
platelet count is desired, especially before surgery.
• There are also advocates for high dose
corticosteroids for additional therapy.
38. • Second-line therapy: involves splenectomy, to
which the majority of patients respond – twothirds will achieve a normal platelet count.
• Patients who do not have a complete
response can still expect some improvement.
39. • Third-line therapy; For those that fail splenectomy,
•
•
a wide range of other therapies are available,
These include;
highdose corticosteroids,
intravenous immunoglobulin,
vinca alkaloids, danazol,
Immunosuppressive agents such as ciclosporin and dapsone.
combination chemotherapy, mycophenolate mofetil.
40. • Major difficulties with many third-line
therapies are modest response rates and slow
onset of action, Consequently ,there is also
interest in the use of specific monoclonal
antibodies such as rituximab, as well as
recombinant thrombopoietin.
41. • However, clinical trials of thrombopoietin were
stopped because of thrombocytopenia but
eltrombopag a thrombopoietin receptor agonist
(which binds to another point of the thrombopoietin
receptor), has been shown to increase platelets in
ITP.
42. • Romiplostim ; a novel thrombopoiesis protein given
weekly subcutaneously, has also been shown to
significantly increase platelet count in ITP on a longterm basis, there were no major adverse effects in
this trial.
• Platelet transfusions are reserved for intracranial or
other extreme haemorrhage, where emergency
splenectomy may be justified.