Transcript 9-CoagulationDisx

Coagulation Disorders
Assistant Professor
Dr Talib Hussein Kamoona (CABM)
Hematologist/Medical Oncologist
Hemostasis
* The intimal surface of blood vessels throughout
the body is lined by monolayer of endothelial cells.
These express anticoagulant properties that
promote blood fluidity normally.
At the site of vascular injury endothelial cells are
activated and converted from antithrombotic to
prothrombotic state or become detached exposing
circulating blood to thrombogenic constituents of
subendothelium.
This results in platelet adhesion that is mediated by
vWF that anchors platelets to blood vessel wall by
binding to platelet GPIb receptors. Then adherent
platelets undergo "release" reaction discharging
constituents of their storage granules such as ADP,
TXA2 which causes further platelets adhesion &
platelet activation.
Activated platelets expose binding sites for fibrin (GP
IIb-IIIa), and then fibrin is formed from plasma
fibrinogen by the action of thrombin. This results
from the activation of coagulation factors cascade
b y either the intrinsic or extrinsic pathways.
Coagulation Cascade
A 10-year-old Caucasian male is to undergo an •
elective tonsillectomy. The pre-operative
history describes significant bleeding after a
recent tooth extraction. The mother reports
that the bleeding occurred several hours after
the tooth extraction, after they had returned
home from the dentist’s office.
What additional questions regarding the patient’s history would be
important to determine if the patient has an underlying coagulopathy?
* Is there a history of bleeding after surgery or
injuries?
* Does the patient suffer from recurrent
infections?
* Was he taking any medication at the time of
his dental extraction, and is he taking any
now?
* Is there a family history of bleeding disorders?
* Is there a history of significant weight loss?
* Evaluation of prior bleeding has been shown to be
predictive of a bleeding disorder. Evaluation of a patient’s
history should focus on spontaneous bleeding, bleeding
after trauma and surgical procedures, and in women, the
presence of menorrhagia.
* Someone who does not have bleeding complications after
trauma or surgical challenges is less likely to have a
significant coagulation disorder.
* Disorders of platelet function or number tend to produce
immediate bleeding after surgical procedures or trauma,
in contrast to disorders of the coagulation system, which
may present as delayed bleeding after initial hemostasis
was obtained.
* Family history, when positive, is also strongly
associated with inherited bleeding disorders,
although genetic coagulation disorders may
also arise from spontaneous gene mutations.
* Since there are many medications that
increase the risk of bleeding, one should take
a history of all prescribed and over-thecounter medications.
* Family history, when positive, is also strongly associated with
inherited bleeding disorders, although genetic coagulation
disorders may also arise from spontaneous gene mutations.
* Since there are many medications that increase the risk of bleeding,
one should take a history of all prescribed and over-the-counter
medications.
* Family history, when positive, is also strongly associated with
inherited bleeding disorders, although genetic coagulation
disorders may also arise from spontaneous gene mutations.
Since there are many medications that increase the risk of bleeding,
one should take a history of all prescribed and over-the-counter
medications.
What aspects of the physical exam do you think
would be most relevant in this case?
* Skin
* Eyes
* Lymph nodes
* Abdomen
* Joints
Which of the following tests should be ordered to
help in the initial evaluation of this patient?
* Complete blood count with differential and
evaluation of blood smear
* Prothrombin time (PT) and partial
thromboplastin time (PTT) with mixing studies
* Bleeding time
* Measurement of von Willebrand activity and
antigen level
Laboratory Test Results
Test
Patient
Normal Range
White blood cell count
6,000/μL
4,500 – 15,000/μL
Hemoglobin
14 g/dL
11.7 – 15.5 g/dL
Platelet count
250,000/μL
150,000 – 400,000/μL
Peripheral smear evaluation
Normal-appearing platelet morphology, no
abnormal white blood cells, normal shape and
distribution of red blood cells
Prothrombin Time (PT)
13.5 sec
12.3 – 14.5 sec
Partial Thromboplastin Time
(PTT)
50 sec
24 – 34 sec
PTT 1:1 mixing study
30 sec
24 – 34 sec
Ristocetin co-factor activity
85%
40% – 200%
von Willebrand antigen
75%
50% – 180%
Given these laboratory results, which of the
following are possible diagnoses in this patient?
* Von Willebrand disease
* Hemophilia A
* Hemophilia B
* Glanzmann’s thrombasthenia
* Platelet storage pool disorder
What factor(s) would you test to diagnose
this disorder?
* Factor VIII
* Factor IX
* Factor XI
* Factor XII
TEACHING POINTS
1. A history of bleeding after previous surgical
procedures or trauma suggests a relatively high
likelihood of an underlying coagulation disorder.
2. It is important to obtain a complete family history,
which may alert you to an inherited coagulation
disorder such as hemophilia A or von Willebrand
disease.
3. The laboratory evaluation of a patient with a
suspected bleeding disorder should be directed by the
findings of the history as well as the physical
examination. An evaluation of the PT, the PTT and the
complete blood count are typically a common starting
point to evaluate the etiology of a patient’s bleeding
symptoms.
TEACHING POINTS
4. Patients with a diagnosis of hemophilia A will typically
have findings and symptoms that are directly related to
the level of factor VIII activity. Patients with less than 5%
of factor VIII activity are more likely to have spontaneous
bleeds into joints (hemarthroses), while less severely
affected patients with higher (but still abnormally low)
factor VIII levels may have bleeding symptoms only after
trauma or surgical procedures.
5. There are other causes of prolonged PTT besides
hemophilia A and B. These include hemophilia C (factor XI
deficiency) and factor XII deficiency. Factors XII and XI are
typically evaluated only if factors VIII and IX are normal.
Hemophilias
Hemophilia A (HA), considered the classic form of the disease,
results from a congenital deficiency of factor VIII (FVIII).
Hemophilia B (HB), also called Christmas disease, is a
consequence of a congenital deficiency of factor IX (FIX)
Hemophilia C (deficiency of factor XI)can be distinguished from
hemophilia A (deficiency of factor VIII) and hemophilia B
(deficiency of factor IX) by the absence of bleeding into
joints and muscles and by its occurrence in individuals of
either sex.
autosomal but not completely recessive because
heterozygotes may have bleeding.
Genetics
X-linked recessive
--- Genes located on long arm of X-chromosome
--- Usually affects males
--- Females are carriers transmitting disease to
sons
--- Female hemophiliacs may be seen in:
* X-chromosome lyonization
* mating between hemophiliac male & female
carrier
* Carrier female with Turner's syndrome
* Carrier with testicular feminization
S&S
--- Severity of bleeding related to level of plasma FVIII
* < 1% activity --- severe disease
* 1-5% activity --- moderate clinical course
--- bleeding in severe cases in early infancy during circumcision
or even during intrauterine life
--- Spontaneous bleeding
--- Acute hemarthroses causing burning or tingling sensation
followed by intense pain & swelling. The joint is swollen, hot &
tender with erythema of the overlying skin. Joint stiffness &
compromised mobility & maintained in a flexed position
* Joint aspiration is not recommended because it may
introduce infection
* FVIII replacement rapidly stops bleeding, resolves
hematoma & improves symptoms
* Recurrent hemarthroses result in chronic synovial
hypertrophy, damage to cartilage, subchondral bone
cyst formation, bony erosion & flexion contractures.
Later OA changes
* Dx by MRI & ultrasound since x-ray may
underestimate the extent of bone & cartilage damage
* Analgesics, rest, avoidance of wt bearing, avoid
NSAIDs
* Synovectomy surgical & non-surgical
* Non-weight bearing exercises
* Joint prosthesis or arthrodesis
* Prevention – planned administration of FVIII 3 times
per week at levels to maintain factor activity at 1-2%
normal
--- Intramuscular hematomas
* follow trauma or IM injection or vaccination
* may compress vital structures
--- Retroperitoneal hematomas
* should be treated aggressively & immediately
--- Mucosal hemorrhage may be seen nose, GIT,
GUT
--- Intracranial bleeding 2nd cause of death after
AIDS
Ask about the patient's family history and bleeding
symptoms.
Male patients with severe hemophilia present at
circumcision.
Easy bruising may occur at the start of ambulation or primary
dentition.
The patient may have a history of hemarthroses and
prolonged bleeding with surgical procedures, trauma,
dental extraction, and he or she may have spontaneous
bleeding in soft tissues.
A traumatic challenge relatively late in life may have to occur
before mild or moderate hemophilia is diagnosed. Factors
that elevate FVIII levels (e.g. stress, exercise) may mask
mild hemophilia. Physiologically low levels of all vitamin K–
dependent procoagulant factors may complicate the early
diagnosis of hemophilia B.
The principal sites of bleeding in patients with
hemophilia are as follows:
For joints, weight-bearing joints and other joints are
affected.
Regarding muscles, those most commonly affected are
the flexor groups of the arms and gastrocnemius of the
legs. Iliopsoas bleeding is dangerous because of the
large volumes of blood loss and because of
compression of the femoral nerve.
In the genitourinary tract, gross hematuria may occur in
as many as 90% of patients.
In the GI tract, bleeding may complicate common GI
disorders.
Bleeding in the CNS is the leading cause of hemorrhagic
death among patients with hemophilia
Physical Exam
Direct the examination to identify signs related to
spontaneous or, with minimal challenge, bleeding
in the joints, muscles, and other soft tissues.
Observe the patient's stature.
Examine the weight-bearing joints, especially the
knees and ankles, and, in general, the large joints
for deformities or ankylosis.
Look for jaundice, other signs of liver failure (eg,
cirrhosis from viral infection), and signs of
opportunistic infections in patients who are HIV
seroconverted
Laboratory Studies
The plasma concentration of FVIII or FIX determines the
severity of hemophilia.
Levels of these factors are assayed against a normal pooled-plasma
standard, which is designated as having 100% activity or the
equivalent of FVIII or FIX 1 U/mL. Patients' tested values ranging
from 50-150% are considered in the normal range of variance.
Aging, pregnancy, contraceptives, and estrogen replacement
therapies are associated with increased levels.
In term and healthy premature neonates, FIX values are lowered
(20-50% of the normal level) and rise to normal levels after 6
months (hepatic immaturity). FVIII levels are normal during that
period of life.
Spontaneous bleeding complications are severe in individuals with
undetectable activity (<0.01 U/mL), moderate in individuals with
activity (2-5% normal), and mild in individuals with factor levels
greater than 5%.
).
Hemophilia A and hemophilia B protein deficiencies
of the intrinsic pathway result in abnormal
whole-blood clotting times, prothrombin times (PTs),
and activated partial thromboplastin times
(aPTTs).
FVIII and FIX activities are usually determined by using
the 1-stage assay based on the aPTT.
Differentiation of hemophilia A from von Willebrand disease is
possible by observing normal or elevated levels of von
Willebrand factor antigen and ristocetin cofactor activity.
Bleeding time is prolonged in patients with von Willebrand
disease but normal in patients with hemophilia.
Laboratory confirmation of a FVIII or FIX inhibitor is clinically
important when bleeding is not controlled after adequate
amounts of factor concentrate are infused during a bleeding
episode.
For autoantibody and alloantibody inhibitors, obtain a repeat
measurement of the patient's prolonged aPTT after incubating
the patient's plasma with normal plasma at 37°C for 1-2 hours.
If the prolonged aPTT is not corrected, use the Bethesda method to
titrate the inhibitor biologic concentration. By convention, more
than 0.6 BU is considered a positive result for an inhibitor, less
than 5 BU is considered a low titer of inhibitor, and more than 10
BU is a high titer (neutralizing effectiveness of factor concentrate
therapy to control bleeding )
℞
--- FVIII replacement
* Severe cases need 50000-80000 IU per year
Level 80-100% for surgery & life threatening bleeds
50% for serious bleeds
25-30% for minor bleeds (hemarthroses & hematuria)
1 IU FVIII / kg body wt = 2% activity increase
3500 IU for 70 kg adult with severe disease needs 100% level
Subsequent dosing every 8-12 hours up to 10-14 days
--- Cryoppt is a rich source of FVIII
--- FFP
--- HB vaccination at an early age
--- HA vaccination
--- Ancillary ttt
* Anti fibrinolytic agents – EACA, tranexamic acid
* DDAVP intravenously or intra nasally
Prevention
Prophylactic replacement of FVIII or FIX is used to maintain a
measurable level at all times, with the goal of avoiding
hemarthrosis and breaking the vicious cycle of repetitive
bleeding and inflammation that results in destructive arthritis.
This goal is achieved by administering factor 2-3 times a week.
The National Hemophilia Foundation has recommended the
administration of primary prophylaxis, beginning at the age of 1-2
years.
Carrier testing may prevent births of individuals with major
hemophilia. This testing can be offered to women interested in
childbearing who have a family history of hemophilia.
Carrier testing is valuable for women who are related to obligate carrier
females or males with hemophilia.
Prenatal diagnosis is important even if termination of the pregnancy is
not desired because a cesarean delivery may be planned or
replacement therapy can be scheduled for the perinatal period.
Disseminated intravascular
coagulation
(DIC)
(defibrination syndrome)
It is a consumptive coagulopathy
that is caused by a wide variety of serious
disorders.
Etiology
* Infections --- G-ve bacterial sepsis
--- Other bacteria, fungi, Rocky Mountain
spotted fever, viruses, malaria
Obstetric complications
--- Amniotic fluid embolism
--- Retained dead fetus
--- Abruptio placentae
--- Toxemia of pregnancy
--- Septic abortion
Malignancies
---- Pancreatic Ca
--- Adenocarcinomas
--- Acute promyelocytic leukemia (M3)
--- Other neoplasms
Trauma
---- Shock
--- Brain injury
--- Crush injury
--- Burns
--- Hypothermia/ Hyperthermia
--- Fat embolism, ischemia, hypoxia
--- Surgery
Vascular disorders
--- Giant hemangiomas (Kassabach-Merritt
syndrome)
--- Vascular tumors, Aortic aneurysms
OTHERS
* Liver failure
* Acute pancreatitis
* Snake venom
* ARDS
* Blood transfusion reaction
Pathogenesis
It is primarily a thrombotic process although its clinical
manifestations may be widespread hemorrhage.
The basic trigger irrespective of etiology is entry into the
circulation of procoagulant substances activating coagulation
factors & platelets leading to disseminated deposition of
fibrin-platelet thrombi. In most cases the procoagulant
stimulant is tissue factor (a lipoprotein that is not normally
exposed to blood), mucin in certain malignancies, proteases
in other malignancies, pancreatitis, and envenomation.
S&S
Asymptomatic --- low grade DIC showing only
Lab abnormalities
Thrombotic complications
--- Trousseau's syndrome
--- Gangrene of digits & extremities
--- Hemorrhagic necrosis of skin
--- Purpura fulminans
Bleeding
--- most common manifestation in acute cases
--- Generalized & widespread
--- Characteristically from the cannula site
--- oozes from mucosal surfaces & orifices
Clinical manifestations of the causative disease
Dx
PT, aPTT & TT are prolonged
Thrombocytopenia,
Plasma Fibrinogen ↓
FDPs ↑ (measured by latex agglutination or Ddimer assay)
Blood film --- Schistocytes, fragmented RBCs
℞
Identify & correct the cause
No treatment --- asymptomatic cases (not ttt lab
manifestations)
Hemodynamic support
Blood component therapy --- FFP, platelets, cryoppt
Drugs --- Inhibitors of coagulation & fibrinolysis
Heparin – theoretic benefit (if thrombosis predominates)
-- may exacerbate bleeding
Antifibrinolytics – EACA & tranexamic acid
-- Generally C/I in DIC
-- may be useful in life-threatening bleeding
Platelet Disorders
Thrombocytopenia
It is a condition in which platelet count is below
normal level.
Causes
1- Aplastic anemia.
2- Leukemia.
3- Tumors metastatic to BM.
4- Myelofibrosis.
5- Megaloblastic anemia.
6- Peripheral platelet destruction
a- Immune
ITP, SLE, PAN, CLL, NHL, infectious mono, CMV infection, HIV,
quinine, quinidine, heparin & sulfa.
b- Non-immune
DIC, TTP, PNH, acute transplant rejection.
7- Disorders of distribution--- Hypersplenism.
8- Dilutional --- Old banked blood transfusion.
Idiopathic Thrombocytopenic Purpura: (ITP)
It is a bleeding disorder caused by autoimmune Abs
destroying patient's own platelets by phagocytosis
in the spleen by Mφ (to a lesser degree in the
liver).
Epidemiology
*Children are affected by an acute type of illness
following URT infection (usually viral).
*♂ = ♀ incidence.
*Adults are affected by a more gradual onset of
disease with chronic course & without preceding
illness.
*Age < 40 years
*♀: ♂ = 3-4:1
S&S
Skin shows petechiae (pinpoint red hemorrhagic
spots) & ecchymoses.
Mucosal bleeding --- bleeding gum, epistaxis,
menorrhagia, metrorrhagia, GI bleeding &
hematuria
Intracranial hemorrhage is seen in 1%. Risk of death
5%
No splenomegaly.
Dx
Platelet count < normal (Thrombocytopenia)
* If > 100000/µL no spontaneous bleeding even
with major surgery
*If 50000-100000/µL Bleeding more than normal
with severe trauma
*If 20000-50000/µL Bleeding occurs with minor
trauma
*If < 20000/µL spontaneous bleeding occurs
*If < 10000/µL patients are at high risk of severe
bleeding
℞
Children have a self-limited disease & 70% recover in
4-6 weeks.
Asymptomatic adult pts with platelet count >
40000/µL are observed periodically & need no ttt
Prednisolone
is the 1st line of ttt 1-2 mg/kg body wt daily
* inhibits Mφ ingestion of Ab-coated platelets
* suppresses Ab synthesis
* have stabilizing effect on blood vessels wall.
-- 80-90% of pts will have rise of platelet count to
hemostatic level within 2-3 weeks
-- Tapered slowly after achieving normal count
Splenectomy
* improves the count in 70% pts & sustained
remission in 60%
* Up to 2 weeks later
* For pts not responding to steroids
* No test can predict which pts can detect which pts
respond to it
Intravenous Immunoglobulin (IVIG)
* Effective in pts with active bleeding & before
major surgery
* Rise platelet count in 3-5 days (The most rapid
agent)
* Blocks receptors to Abs on Mφ therefore
inhibiting phagocytosis
* High dose needed 1g/kg B wt/day on 2 successive
days
* Very expensive
* Its effect is unfortunately transient
Danazol
(Danol)
* 200mg three times per day
* Induces remission in 40% of cases
* Response is delayed 4-6 weeks
* Impeded androgen
* Mechanism of action remains unknown
Vincristine (Oncovin) & Vinblastine
(Velbe)
* Cytotoxic drugs
* Given IV
* Raise platelet within 1-2 weeks
* Transient & nonsustained response
Immunosuppressants
Cyclophosphamide & Azathioprine
* Improve platelet count in 20-30% of cases
* Risk of toxicity has to be weighed against
potential benefit
ITP in Pregnancy
* Complicated by additional risk to the fetus
(thrombocytopenia due to maternal Abs) ,
newborn intraventricular hemorrhage & GI
bleeding
* C/S delivery is recommended to decrease risk
of intracranial bleeding in the newborn.
Functional platelet disorders
Hereditary
Glanzmann's thrombasthenia •
Bernard-Soulier syndrome •
Storage pool disease •
ITP
Thrombotic Dis
Hypercoagulable States
are more likely to develop clots,venous and
arterial thrombosis than healthy individuals.
There is often a history of recurrent
thromboembolism, thrombosis at a young
age, pulmonary embolism and a family history
of thrombosis. Venous thrombosis and are
associated with significant morbidity and
mortality.
Causes
Hereditary – Antithrombin III def •
- Protein C def
- Protein S def
- FV Leiden
Acquired
Acquired
Advanced age
Immobilization
Inflammation
Pregnancy
Oral contraception use
Obesity
Diabetes
Hormonal replacement therapy
Cancer (especially adenocarcinoma)
Lupus anticoagulant
Sickle cell anemia and other hemolytic anemias
Pathophysiology
The Virchow triad of underlying factors in
venous thrombosis include hypercoagulability,
venous stasis, and vascular damage. The risk
factors mentioned above tip the balance of
Virchow’s triad. Procoagulants are released in
patients with cancer. Immobilization, obesity,
and advanced age lead to reduced blood flow
and venous stasis.
pregnancy
Thrombosis during pregnancy can be due to
increased procoagulant factors, impaired
fibrinolysis, venous stasis, and endothelial cell
injury.[2] The risk of thrombosis is increased in
patients on hormonal replacement therapy.
Prevalence in population
Condition
Prevalence in
General
Population, %
Relative Risk of
VTE, %
Relative Risk of
Recurrent VTE, %
Factor V Leiden
3-7
4.3
1.3
Prothrombin
20210A
1-3
1.9
1.4
Protein C
0.02-0.05
11.3
2.5
Protein S
0.01-1
32.4
2.5
0.02-0.04
17.5
2.5
Antithrombin III
Mortality/Morbidity
Morbidity and mortality in patients with hypercoagulable states and
thrombophilia are primarily due to venous thrombosis and
pulmonary embolism. Pulmonary embolism is associated with a 13% mortality rate. The incidence of factor V Leiden and
prothrombin 20210A is significantly greater than that of protein C,
protein S, and antithrombin III (ATIII) deficiencies. However, the risk
of venous thrombosis in protein C, protein S, and antithrombin III
(ATIII) deficiencies is greater than in factor V Leiden and
prothrombin 20210A, as shown in Table above.
The risk for thrombosis can be markedly increased in patients with 2 or
more risk factors for thrombosis. Any multiplicity of risk factors,
albeit hereditary thrombophilias or acquired risks, increase the risk
for thrombosis.
Hereditary thrombophilia
These disorders should be suspected in patients has a history of
recurrent venous thromboembolism, venous thrombosis in a
person younger than 40 years, a familial history of venous
thromboembolism, and thrombosis in unusual sites (eg, mesenteric
vein, renal vein, hepatic and cerebral thrombosis).
Purpura fulminans in infancy could suggest protein C deficiency.
Thrombophilic disorders are usually associated with venous
thrombosis. However, protein S, protein C, ATIII deficiencies, and
lupus anticoagulants have been associated with arterial
thrombosis.
Patients with protein C and S deficiencies can develop warfarininduced skin necrosis when placed on warfarin since protein C and S
are vitamin K–dependent factors and, hence are suppressed.
Lupus anticoagulants
These antibodies occur in about 20% of patients with systemic lupus
erythematosus (SLE), but they are also associated with other
autoimmune diseases. Lupus anticoagulants may occur in patients
taking phenothiazines, phenytoin, phenytoin, hydralazine, quinine,
amoxicillin, and oral contraceptives.
Clinical criteria for indicating the presence of lupus anticoagulants
(Sapporo criteria for the antiphospholipid syndrome) are as
follows:
One or more arterial, venous, or small vessel thrombosis, affecting any
organ or tissue
Pregnancy morbidity: The risk for maternal and fetal morbidity
increases after the 10th week of pregnancy. Fetal mortality in
pregnancy can include spontaneous abortions, prematurity, and
stillbirths.
Three or more unexplained consecutive spontaneous abortions after
the 10th week of gestation
Lab
PT ; aPTT; INR
D-dimer assay
Anti-cardiolipin Ab
treatment
Heparin
LMWH
Warfarin
Fondaparinux
Case2
A 20-year-old college student returned to the U.S.
following a summer break in which she traveled and
hiked extensively in New Zealand.
Two days after her flight she awoke with swelling and
pain in her left calf and thigh and noticed that the
skin of the leg appeared dusky blue in color.
Because of these rather alarming symptoms, and the
fact that her mother had a blood clot when she was
young, she came immediately to the emergency
room where noninvasive venous studies showed an
extensive deep venous thrombosis involving the
popliteal, femoral and iliac veins on the left.
Should this patient be evaluated for an
underlying thrombophilia?
* Yes
* No
Common Risk Factors for Thrombosis
Obesity
Inactivity
Pregnancy
Estrogens/Birth Control Pills
Post-surgery
Malignancy
Inherited Procoagulant States
Defect
Incidence in Population Percent of Patients with
Procoagulant States
1. Factor V Leiden
5-10%
20-60%
2. Prothrombin Gene Mutation
2-4%
6-8%
3. Protein C Deficiency
1:200
<5%
4. Protein S Deficiency
--
<5%
5. Antithrombin Deficiency
1:2-5,000
<1%
6. Dysfibrinogenemia
Not known
~1-2%
7. Elevated Lipoprotein(a)
Not known*
--
Acquired Prothrombotic Medical
States
Antiphospholipid antibody syndrome
Disseminated intravascular coagulation
Heparin-induced thrombocytopenia and
thrombosis syndrome
Inflammatory bowel disease
Myeloproliferative disorders
Nephrotic syndrome
Paroxysmal nocturnal hemoglobinuria (PNH)
What symptoms or history might be
helpful in making the diagnosis?
Do you have any illnesses?
Have you ever had a thrombosis in the past?
Has anyone else in your family had a thrombosis?
Have you ever experienced leg cramps while hiking?
What medications are you on?
Was this your first trip overseas?
Have you ever been pregnant?
Select the factors that may have
predisposed her to a venous
thrombosis.
Birth control pills
Inherited hypercoagulable state.
Long airplane ride
Low airplane cabin pressure
Vigorous exercise
Vitamin C use
Trauma
Which of the following laboratory
examinations should be ordered?
* Complete Blood Count with platelets
* aPTT (activated partial thromboplastin time) and
PT (prothrombin time)
* Antithrombin activity and antigen
* Protein C activity and antigen
* Free Protein S antigen
* Factor V Leiden gene polymorphism
* Anticardiolipin and anti-ß2-glycoprotein 1
antibodies and lupus anticoagulant assays
* Prothrombin 20210 gene polymorphism
Which of these additional labs should
be ordered?
Activated Protein C Resistance Assay
Coagulation Factor VIII (*FVIII:C)
Fibrinogen activity and antigen
Tissue Plasminogen Activator activity
Lipoprotein(a)
Which one of the following laboratory
tests reveals an abnormality?
Complete Blood Count
Beta-HCG
Antithrombin III activity
Protein C activity
Protein S activity
Prothrombin Gene mutation
Homocysteine
Anticardiolipin Antibody
Lupus Inhibitor Evaluation
Select the most appropriate
treatment option for this patient.
* Six weeks of oral anticoagulant therapy
* Six months of oral anticoagulant therapy
* Extended duration anticoagulation
Should her family be screened for
protein C deficiency?
* No
* Yes
The patient's sister was found to be heterozygous for
protein C deficiency. She has asked your advice about
the risks of pregnancy. What do you tell her?
* The risks are minimal.
* She is at increased risk for thrombosis during
pregnancy and otherwise.
The patient's sister (who has asymptomatic protein C
deficiency) has also asked your advice about taking oral
contraceptives. Select the most appropriate advice.
* Oral contraceptives are an acceptable choice
given the low risk of thrombosis.
* She should consider alternate forms of
contraception.
Four clues to a hypercoagulable state
* Thrombosis at an early age
* Recurrent thromboses
* Thrombosis at an unusual site
* Family history of thrombosis
Five most common inherited
prothrombotic states
Factor V Leiden
Hyperhomocysteinemia
Prothrombin gene mutation
Protein S deficiency
Protein C deficiency
At least five acquired hypercoagulable
states
* Estrogen excess (oral contraceptives,
pregnancy)
* Malignancy
* Antiphospholipid antibodies
* Inflammatory Bowel Disease
* Nephrotic syndrome