DISORDERS OF
HEMOSTASIS
Dept.of Hematology ZhongShan
Hospital,FuDan University
Prof,JlAN-MIN XU
General Considerations
? Disorders of hemostasis
defects in platelet number or function
problems in fibrin clot (coagulation)
? Bleeding due to platelet disorders is
typically mucosal or dermatologic
include epistaxis,gum bleeding,
menorrhagia,gastrointestinal bleeding,
purpura,and petechiae
Thrombocytopenic
Purpura
Dept.of Hematology ZhongShan
Hospital,FuDan University
Prof,JlAN-MIN XU
Brief
1.definition,bleeding of skin,mucous and
organs
2.cause,
（ 1） production, drug,tumor,infection,
radiation
（ 2） destruction, ITP,DIC,TTP
（ 3） abnormal distribution,splenomegaly
3.classification,primary,secondary
IDIOPATHIC (AUTOIMMUNE)
THROMBOCYTOPENIC
PURPURA (ITP)
General Considerations
? ITP is an autoimmune disorder in which
an IgG autoantibody is formed that
binds to platelets
? It is not clear which antigen on the
platelet surface is involved,
? Although the antiplatelet antibody may
bind complement,platelets are not
destroyed by direct lysis
General Considerations
? Rather,destruction takes place in the
spleen,where splenic macrophages
with Fc receptors bind to antibody-
coated platelets
? Since the spleen is the major site both
of antibody production and platelet
sequestration,splenectomy is highly
effective therapy
General Considerations
1.definition,thrombocyte unrelated to a
drug,an infection,or autoimmune
disease is generally classified as ITP
2.character,
shortened span of platelet
increased megakaryocyte in bone
marrow
3.classification,acute,chronic
Mechanism
1.Immunity
（ 1） acute,
postviral infection
immune complex (viral Ag and Ab)
connect with platelet Fc-R
viral components banding with platelet
auto Ab generation
（ 2） chronic,not affected by foreign Ag
Mechanism
2.liver and spleen,
（ 1） 1/3 platelets are held within the spleen
（ 2） spleen produces platelet associated Ab
（ 3） liver and spleen erase platelet,7-11 days
in normal persons,1-3 days in patients
Mechanism
3.else,
（ 1） estrogen,
ITP often seen in female patient
hold down platelet production
augment platelet clearance
（ 2） more delicate capillary wall
Clinical Findings
? Symptoms and Signs,
? occurs,
in childhood,frequently precipitated by
viral infection and usually self-limited,
In adult form is usually a chronic
disease and only infrequently follows a
viral infection,
Clinical Findings
? age,
It is a disease of young persons,with
peak incidence between ages 20 and 50
? sex,
there is a 2:1 female predominance
Clinical Findings
? presenting complaint,
mucosal or skin bleeding,
Common types,
epistaxis,oral bleeding,menorrhagia,
purpura,and petechiae,
? Patients are systemically well and not
febrile,
Clinical Findings
? On examination,
no abnormal findings other than those
related to bleeding,
An enlarged spleen should lead one to
doubt the diagnosis,
Common signs of bleeding are purpura,
petechiae,and hemorrhagic bullae in
the mouth,
Clinical Findings
1,occurs,
（ 1） acute,
children,fever
viral infection history
fervent uprise,
（ 2） chronic,
young or middle-aged female
dormant uprise
Clinical Findings
2,bleeding,
（ 1） manifestation,
a,petechial and purpuric,epistaxis
gum bleeding
b,menorrhagia,digestive tract,
urotract bleeding
c,retina hemorrhage— blindness
intracranial hemorrhage--death
Clinical Findings
（ 2） characteristic,
a,acute,severe,self-limited (4-6w）
seldom relapse
b,chronic,less severe,ofter relapse
longterm
3,else,anemia (severe bleeding)
mild splenomegaly
Laboratory Findings
? Laboratory Findings,
? Peripheral blood,
counts,
The hallmark is thrombocytopenia,which
may be less than 10,000/mL,
Other counts are usually normal except for
occasional mild anemia
Laboratory Findings
? cell morphology,
normal except that platelets are slightly
enlarged (megathrombocytes),
These larger platelets are young platelets
produced in response to enhanced platelet
destruction,
Laboratory Findings
? Evans‘s syndrome,
Approximately 10% of patients will have
coexistent autoimmune hemolytic anemia
will see anemia,reticulocytosis,and
spherocytes on peripheral smear,
Red blood cell fragmentation should not
be seen,
Laboratory Findings
? bone marrow,
appear normal,with a normal or increased
number of megakaryocytes,
? Tests,
Coagulation studies will be entirely normal,
Quantitate platelet-associated IgG may
help the diagnosis,highly sensitive (95%)
but very nonspecific(50%)
Essentials of Diagnosis
? Isolated thrombocytopenia,
? Other hematopoietic cell lines normal,
? No systemic illness,
? Spleen not palpable,
? Normal bone marrow with normal or
increased megakaryocytes
Differential Diagnosis
? Thrombocytopenia may be produced
either by abnormal bone marrow function
or by peripheral destruction,
? bone marrow disorders,
diagnoses such as myelodysplasia can
only be excluded by examining the bone
marrow,
Differential Diagnosis
? peripheral destruction,
Can be ruled out by initial evaluation,
Disorders such as DIC,TTP,HUS、
hypersplenism,and sepsis are easily
excluded by the absence of systemic
illness,
Patients with isolated thrombocytopenia
with no other abnormal findings almost
certainly have immune thrombocytopenia,
Differential Diagnosis
Patients should be questioned regarding
drug use,especially sulfonamides,quinine,
thiazides,cimetidine,gold,and heparin,
Heparin is now the most common cause of
drug-induced thrombocytopenia in
hospitalized patients,
SLE,Cll are common causes of
secondary thrombocytopenic purpura,
hematologically identical to ITP,
Treatment
? Few adults with ITP will have spontaneous
remissions,most will require treatment,
? Prednisone,
Primarily by decreasing the affinity of
splenic macrophages for antibody-coated
platelets,High-dose also reduces the
binding of antibody to the platelet surface,
Long-term therapy decrease antibody
production
Treatment
? Initial treatment is 1–2 mg/kg/d,
? Bleeding will often diminish within 1 day
? The platelet count will usually begin to rise
within a week
? Responses are almost always seen within
3 weeks,
? About 80% of patients will respond,and
the platelet count will usually return to
normal,
Treatment
? High-dose therapy should be continued
until the platelet count is normal,and the
dose should then be gradually tapered,
? In most,thrombocytopenia will recur if
prednisone is completely withdrawn,and
one aims to find a dose that will maintain
an adequate platelet count,
Treatment
? It is not necessary for the platelet count to
be entirely normal
? the risk of bleeding is small with platelet
counts above 50,000/mL,
Treatment
? Splenectomy,
the most definitive treatment for ITP,and
most adult patients will ultimately undergo
splenectomy
High-dose prednisone therapy should not
be continued indefinitely in an attempt to
avoid surgery,
Treatment
? Indicated,
If patients do not respond to prednisone
initially or require unacceptably high doses
to maintain an adequate platelet count,
Other patients may be intolerant of
prednisone or may simply prefer the
surgical alternative,
Treatment
? Safety,
performed safely even with platelet counts
less than 10,000/mL,
? Efficacy,
Eighty percent of patients benefit from
splenectomy with either complete or partial
remission,
Treatment
? High-dose intravenous immunoglobulin
Reserved for bleeding emergencies or
situations such as preparing a severely
thrombocytopenic patient for surgery
This treatment is expensive
Treatment
400 mg/kg/d for 3–5 days
highly effective in rapidly raising the
platelet count,
The response rate is 90%
The platelet count rises within 1–5 days,
The beneficial effect lasts only 1–2 weeks,
Treatment
? Danazol,
patients who fail to respond to prednisone
and splenectomy,600 mg/d,with
responses obtained in about half of cases,
? Immunosuppressive agents,
employed in refractory cases
include vincristine,vinblastine infusions,
azathioprine,cyclosporine,and
cyclophosphamide,
Treatment
? Platelet transfusions,
Rarely used in the treatment of ITP
Since exogenous platelets will survive no
better than the patient's own and will
survive less than a few hours,
Platelet transfusion reserved for cases of
life-threatening bleeding in which even
fleeting hemostasis may be of benefit,
Prognosis
? The prognosis for remission is good,
? In most cases,the disease is initially
controlled with prednisone
? splenectomy offers definitive therapy,
Prognosis
? The major concern during the initial
phases is cerebral hemorrhage,which
becomes a risk when the platelet count is
less than 5000/mL,
? These patients usually exhibit warning
signs of mucosal bleeding,
? However,even at these very low platelet
counts,fatal bleeding is rare,
HEMOSTASIS
Dept.of Hematology ZhongShan
Hospital,FuDan University
Prof,JlAN-MIN XU
General Considerations
? Disorders of hemostasis
defects in platelet number or function
problems in fibrin clot (coagulation)
? Bleeding due to platelet disorders is
typically mucosal or dermatologic
include epistaxis,gum bleeding,
menorrhagia,gastrointestinal bleeding,
purpura,and petechiae
Thrombocytopenic
Purpura
Dept.of Hematology ZhongShan
Hospital,FuDan University
Prof,JlAN-MIN XU
Brief
1.definition,bleeding of skin,mucous and
organs
2.cause,
（ 1） production, drug,tumor,infection,
radiation
（ 2） destruction, ITP,DIC,TTP
（ 3） abnormal distribution,splenomegaly
3.classification,primary,secondary
IDIOPATHIC (AUTOIMMUNE)
THROMBOCYTOPENIC
PURPURA (ITP)
General Considerations
? ITP is an autoimmune disorder in which
an IgG autoantibody is formed that
binds to platelets
? It is not clear which antigen on the
platelet surface is involved,
? Although the antiplatelet antibody may
bind complement,platelets are not
destroyed by direct lysis
General Considerations
? Rather,destruction takes place in the
spleen,where splenic macrophages
with Fc receptors bind to antibody-
coated platelets
? Since the spleen is the major site both
of antibody production and platelet
sequestration,splenectomy is highly
effective therapy
General Considerations
1.definition,thrombocyte unrelated to a
drug,an infection,or autoimmune
disease is generally classified as ITP
2.character,
shortened span of platelet
increased megakaryocyte in bone
marrow
3.classification,acute,chronic
Mechanism
1.Immunity
（ 1） acute,
postviral infection
immune complex (viral Ag and Ab)
connect with platelet Fc-R
viral components banding with platelet
auto Ab generation
（ 2） chronic,not affected by foreign Ag
Mechanism
2.liver and spleen,
（ 1） 1/3 platelets are held within the spleen
（ 2） spleen produces platelet associated Ab
（ 3） liver and spleen erase platelet,7-11 days
in normal persons,1-3 days in patients
Mechanism
3.else,
（ 1） estrogen,
ITP often seen in female patient
hold down platelet production
augment platelet clearance
（ 2） more delicate capillary wall
Clinical Findings
? Symptoms and Signs,
? occurs,
in childhood,frequently precipitated by
viral infection and usually self-limited,
In adult form is usually a chronic
disease and only infrequently follows a
viral infection,
Clinical Findings
? age,
It is a disease of young persons,with
peak incidence between ages 20 and 50
? sex,
there is a 2:1 female predominance
Clinical Findings
? presenting complaint,
mucosal or skin bleeding,
Common types,
epistaxis,oral bleeding,menorrhagia,
purpura,and petechiae,
? Patients are systemically well and not
febrile,
Clinical Findings
? On examination,
no abnormal findings other than those
related to bleeding,
An enlarged spleen should lead one to
doubt the diagnosis,
Common signs of bleeding are purpura,
petechiae,and hemorrhagic bullae in
the mouth,
Clinical Findings
1,occurs,
（ 1） acute,
children,fever
viral infection history
fervent uprise,
（ 2） chronic,
young or middle-aged female
dormant uprise
Clinical Findings
2,bleeding,
（ 1） manifestation,
a,petechial and purpuric,epistaxis
gum bleeding
b,menorrhagia,digestive tract,
urotract bleeding
c,retina hemorrhage— blindness
intracranial hemorrhage--death
Clinical Findings
（ 2） characteristic,
a,acute,severe,self-limited (4-6w）
seldom relapse
b,chronic,less severe,ofter relapse
longterm
3,else,anemia (severe bleeding)
mild splenomegaly
Laboratory Findings
? Laboratory Findings,
? Peripheral blood,
counts,
The hallmark is thrombocytopenia,which
may be less than 10,000/mL,
Other counts are usually normal except for
occasional mild anemia
Laboratory Findings
? cell morphology,
normal except that platelets are slightly
enlarged (megathrombocytes),
These larger platelets are young platelets
produced in response to enhanced platelet
destruction,
Laboratory Findings
? Evans‘s syndrome,
Approximately 10% of patients will have
coexistent autoimmune hemolytic anemia
will see anemia,reticulocytosis,and
spherocytes on peripheral smear,
Red blood cell fragmentation should not
be seen,
Laboratory Findings
? bone marrow,
appear normal,with a normal or increased
number of megakaryocytes,
? Tests,
Coagulation studies will be entirely normal,
Quantitate platelet-associated IgG may
help the diagnosis,highly sensitive (95%)
but very nonspecific(50%)
Essentials of Diagnosis
? Isolated thrombocytopenia,
? Other hematopoietic cell lines normal,
? No systemic illness,
? Spleen not palpable,
? Normal bone marrow with normal or
increased megakaryocytes
Differential Diagnosis
? Thrombocytopenia may be produced
either by abnormal bone marrow function
or by peripheral destruction,
? bone marrow disorders,
diagnoses such as myelodysplasia can
only be excluded by examining the bone
marrow,
Differential Diagnosis
? peripheral destruction,
Can be ruled out by initial evaluation,
Disorders such as DIC,TTP,HUS、
hypersplenism,and sepsis are easily
excluded by the absence of systemic
illness,
Patients with isolated thrombocytopenia
with no other abnormal findings almost
certainly have immune thrombocytopenia,
Differential Diagnosis
Patients should be questioned regarding
drug use,especially sulfonamides,quinine,
thiazides,cimetidine,gold,and heparin,
Heparin is now the most common cause of
drug-induced thrombocytopenia in
hospitalized patients,
SLE,Cll are common causes of
secondary thrombocytopenic purpura,
hematologically identical to ITP,
Treatment
? Few adults with ITP will have spontaneous
remissions,most will require treatment,
? Prednisone,
Primarily by decreasing the affinity of
splenic macrophages for antibody-coated
platelets,High-dose also reduces the
binding of antibody to the platelet surface,
Long-term therapy decrease antibody
production
Treatment
? Initial treatment is 1–2 mg/kg/d,
? Bleeding will often diminish within 1 day
? The platelet count will usually begin to rise
within a week
? Responses are almost always seen within
3 weeks,
? About 80% of patients will respond,and
the platelet count will usually return to
normal,
Treatment
? High-dose therapy should be continued
until the platelet count is normal,and the
dose should then be gradually tapered,
? In most,thrombocytopenia will recur if
prednisone is completely withdrawn,and
one aims to find a dose that will maintain
an adequate platelet count,
Treatment
? It is not necessary for the platelet count to
be entirely normal
? the risk of bleeding is small with platelet
counts above 50,000/mL,
Treatment
? Splenectomy,
the most definitive treatment for ITP,and
most adult patients will ultimately undergo
splenectomy
High-dose prednisone therapy should not
be continued indefinitely in an attempt to
avoid surgery,
Treatment
? Indicated,
If patients do not respond to prednisone
initially or require unacceptably high doses
to maintain an adequate platelet count,
Other patients may be intolerant of
prednisone or may simply prefer the
surgical alternative,
Treatment
? Safety,
performed safely even with platelet counts
less than 10,000/mL,
? Efficacy,
Eighty percent of patients benefit from
splenectomy with either complete or partial
remission,
Treatment
? High-dose intravenous immunoglobulin
Reserved for bleeding emergencies or
situations such as preparing a severely
thrombocytopenic patient for surgery
This treatment is expensive
Treatment
400 mg/kg/d for 3–5 days
highly effective in rapidly raising the
platelet count,
The response rate is 90%
The platelet count rises within 1–5 days,
The beneficial effect lasts only 1–2 weeks,
Treatment
? Danazol,
patients who fail to respond to prednisone
and splenectomy,600 mg/d,with
responses obtained in about half of cases,
? Immunosuppressive agents,
employed in refractory cases
include vincristine,vinblastine infusions,
azathioprine,cyclosporine,and
cyclophosphamide,
Treatment
? Platelet transfusions,
Rarely used in the treatment of ITP
Since exogenous platelets will survive no
better than the patient's own and will
survive less than a few hours,
Platelet transfusion reserved for cases of
life-threatening bleeding in which even
fleeting hemostasis may be of benefit,
Prognosis
? The prognosis for remission is good,
? In most cases,the disease is initially
controlled with prednisone
? splenectomy offers definitive therapy,
Prognosis
? The major concern during the initial
phases is cerebral hemorrhage,which
becomes a risk when the platelet count is
less than 5000/mL,
? These patients usually exhibit warning
signs of mucosal bleeding,
? However,even at these very low platelet
counts,fatal bleeding is rare,
