Hemostasis is a balancing act between clot formation and fibrinolysis or clot dissolution.
-In injuries, the exposure of collagen in the basement membrane stimulates platelets adhesion ---change in platelets shape ---- platelets reaction (TxA2,ADP, ATP, serotonin & active agents ) ----- vasoconstriction & further platelet aggregation ------- platelet plug. -Fibrin formation is the end product of enzymatic reaction , conducted by both extrinsic & intrinsic pathways. -
Thrombin converts fibrinogen to fibrin monomer by initially cleaving fibrinopeptides A and B. After a loosely cross-linked fibrin clot is formed, FXIIIa is able to cross-link fibrin, leading to clot stabilization.
The process of fibrinolysis enables cross-linked clots to be degraded. The fibrinolytic process involves the zymogen plasminogen, which is converted to plasmin by tPA or uPA. PAI-1 and 2-antiplasmin are the physiologic inhibitors of plasminogen activator and plasmin, respectively.
this hypercoagulable state with local activation of clotting system is associated with increased risk of not only VTE but also DIC
The fibrinolytic system is responsible for disposing of fibrin after fulfilling its haemostatic function Plasma proteases are responsible for controlling the speed and extent of coagulation & fibrinolysis
Quantitative-Thrombotic thrombocytopenic purpura,Hemolytic uremic syndrome, Qualitative-Glanzmann&apos;s thrombasthenia,Bernard-Soulier syndrome(abnormal glycoprotein Ib-IX-V complex),Storage pool disorders,Paroxysmal nocturnal hemoglobinuria ,Gray platelet syndrome deficient alpha granules.,Delta storage pool deficiency: deficient dense granules. Disorders predisposing to thrombosis Antiphospholipid syndrome Lupus anticoagulant Anticardiolipin antibody ,Heparin-induced thrombocytopenia,Factor V Leiden and Activated Protein C Resistance ,Prothrombin mutation ,Protein C deficiency ,Protein S deficiency ,Antithrombin deficiency ,Abnormally raised levels of Factor VIII and Factor XI
The next inherited bleeding disorder which are uncommon in females are: hemophilia A: which is due to factor VIII deficiency and it is an X-linked recessive and females are usually carrier for the disease, rarely the female may be affected. -Hemophilia B is also known as Christmas disease; it is factor IX deficiency. Again, it is an X-linked recessive and it is much less common than hemophilia A.
Patients with hemophilia A or B, because of prior treatment with factor VIII or IX, may develop antibodies directed against factor VIII or IX and may lead to life-threatening hemorrhage. more commonly develop such antibodies. In contrast, acquisition of these antibodies in nonhemophiliacs is rare. This phenomenon has also been identified rarely in women during the puerperium (Santoro and Prejano, 2009). In these cases, the prominent clinical feature is severe, protracted, repetitive hemorrhage from the reproductive tract starting a week or so after an apparently uncomplicated delivery (Reece and associates, 1988). The activated partial thromboplastin time is markedly prolonged. Treatment has included multiple transfusions of whole blood and plasma; huge doses of cryoprecipitate; large volumes of an admixture of activated coagulation factors, including porcine factor VIII; immunosuppressive therapy; and attempts at various surgical procedures, especially curettage and hysterectomy. Another treatment involves bypassing factor VIII or IX by the use of activated forms of factors VII, IX, and X. A recombinant activated factor VII
Prothrombin, under the right conditions, is converted to thrombin, which activates fibrin and begins the process of coagulation
-Often the patients are asymptomatic and pregnancy does not always exacerbate the disease. -If platelet count is more than 50x 10/L no treatment is necessary.
Out of pre- eclampsia’s various manifestations, a specific entity is HELLP syndrome.
Periportal or focal parenchymal necrosis in which hyaline deposits of fibrin like material lead to Obstruction of hepatic blood flow Hemolysis is due to a microangiopathic haemolytic anaemia (MAHA). Platelets are activated, and adhere to damaged vascular endothelial cells, resulting in increased platelet turnover with shorter lifespan. Decreased Platelet count in the HELLP syndrome is due to their increased consumption.
Thrombocytopenia occurs first followed by raised liver enzymes and last is hemolysis If DIC is not present – PT , aPPT, S. Fibrinogen will be normal If fibrinogen &lt; 300 mg/dl along with other lab abnormality – DIC is suspected Positive D-dimer test is more sensitive indicator of sub clinical coagulopathy and may be positive before other coagulation studies are abnormal. Proteinuria
In general, there are three major options for the management of women with severe preeclampsia and HELLP syndrome These include: . In this situation, Steroid treatment is often used, Platelet transfusion – is required eithr before or after delivery, in presence of bleeding from puncture site, wound and intra peritoneal bleeding. PCV and FFP – required if coagulopathy is present
The acquired disorders that lead to bleeding. These include DIC, vitamin K deficiency, liver disease, uremia and after massive transfusion
PROFILE IN OBSTETRIC PATIENTS
Dr. Kirti S. Ruikar
Obstetrics is "bloody business." Although
medical advances have dramatically reduced
the dangers of childbirth, death from
haemorrhage still remains a leading cause of
Hemorrhage is the single most important
cause of maternal death worldwide.
Obstetrical hemorrhage accounts for almost
half of all postpartum deaths in developing
Refresh about the normal coagulation
cascade mechanisms and its triggers
To understand the alterations in
coagulations & Fibrinolysis associated
Broad line classification of coagulation
failure in pregnancy
To get brief knowledge on some
important causes of deranged
coagulation in pregnancy
Understanding the pathogenesis of DIC
syndrome, diagnosis, complications &
Haemostasis balancing act
-Vascular endothelium releases a potent antiplatelet
agent called prostacyclin (PGI2) which limits the size
of any micro thrombi formed , so it prevents overt
-On the other hand the platelets release
thromboxane A2 (TxA2) which performs a powerful
platelet aggregation .
-If there is any imbalance between PGI2 & TxA2 , the
result can be a predisposition of either bleeding or
Primary + Secondary + Tertiary
Platelet Plug Formation:dependent on normal
platelet number & function
Activation of Clotting Cascade Deposition &
Stabilization of Fibrin
Dissolution of Fibrin Clot:dependent on Plasminogen
Normal haemostasis & the vascular tree
The normal function of coagulation & fibrinolytic
system is to maintain an intact but patent
Three main components play a part in normal
• The fibrinolytic system is complementary to these
activities & is responsible for the removal of fibrin &
the restoration of vascular patency.
HOW DOES THE PROCESS OF
Three pathways of blood coagulation are
In addition to the clotting factors there are
many substances that inhibit coagulation:
-Anti- thrombin III (AT III)
-Alpha 2 globulin inhibits Thrombin & factors Xa, XIIa
,XIa and IXa.
-Protein C (endothelial cell )
-Protein S (endothelial cell & platelets )
Coagulation & fibrinolytic
system during pregnancy
-Placental separation during the 3rd stage of labour
represents a major haemostatic challenge to the
-Physiological adaptations occur during pregnancy
to help the mother meet this haemostatic
-Together the change in coagulation & fibrinolysis in
pregnancy represents a hypercoagulable state .
Coagulation system during pregnancy
-Plasma fibrinogen concentrations rise during pregnancy by
about 50% , this means that double the amount of
fibrinogen is available to pregnant woman at delivery .
-Concentration of other clotting factors also rise , especially
Prothrombin & factors V ,VII , VIII . IX , X , & XII.
-Notable exception are factors XI & XIII ,whose concentrations
fall during pregnancy.
-Despite the increased potential to form thrombin in
pregnancy , there is no compensatory rise in
-Platelet count shows little , if any , change.
-Plasma plasminogen levels rise in tandem with the
rise of fibrinogen.
-Anti plasmins also rise so that the capacity to
generate plasmin may be reduced in pregnancy .
Fibrinolytic system during pregnancy
Coagulation & fibrinolysis during
-Following delivery , major changes occur in the coagulation &
-Rise in plasminogen activator activity which return to non
pregnant range within 30 min of delivery .
-Fibrinogen level & platelets count rise during early
-Anti- thrombin activity increase.
-Following the initial phase o f increased clotting factors in the
puerperium ,the coagulation & fibrinolytic system gradually
revert to normal within 6 weeks after delivery.
Coagulation changes in
Bleeding during labour is dealt with effectively by
- increased production of coagulation
factors during pregnancy
- increased blood volume
- myometrial contraction
coagulation disorders in
Haemophilia A and B
Retained dead fetus
Amniotic fluid embolus
Anticoagulants: Aspirin and heparin
Screening tests for hemostasis
TESTS OF PRIMARY HEMOSTASIS
Bleeding time Platelet and vascular phases
PFA-100 system Platelet function
Platelet count Quantitation of platelets
Blood smear 1.Quantitative and morphological
abnormalities of platelets
2.Detection of underlying haematological
TESTS OF SECONDARY HEMOSTASIS
Clotting time Crude test of coagulation phase
Prothrombin time Extrinsic and common pathways
Activated partial thromboplastin time Intrinsic and common pathways
PROVIDES ASSESSMENT OF PLATELET
COUNT AND FUNCTION
NORMAL 150,000 - 400,000 CELLS/MM3
< 100,000 Thrombocytopenia
50,000 - 100,000 Mild Thrombocytopenia
< 50,000 Severe Thrombocytopenia
INR: International normalized ratio
- Established by the WHO and the International Committee on
Thrombosis and Haemostasis for reporting the results of
-All PT results are standardized by this calculation:
INR = ( Patient PT / Control PT) ISI
ISI= International sensitivity index
- Given by the manufacturer for each particular thromboplastin
reagent and instrument combination
of the Intrinsic
pathway & common pathway
NORMAL VALUENORMAL VALUE
25-40 SECS25-40 SECS
Tests for specific Platelet Functions
1. Platelet aggregation test
2. Flow cytometry
3. Test for platelet secretion
4. Clot retraction test
5. Platelet pro-coagulant activity
Test for Coagulation Phase
1. Quantitative estimation of Fibrinogen
2. Coagulation factor assays
3. F XIII Qualitative assay
Latex agglutination test for Fibrinolysis
Von Willebrand Disease
Von Willebrand Disease
Symptomatic patients usually present with evidence
of a platelet defect
Considered in women with bleeding suggestive of a
chronic disorder of coagulation.
During normal pregnancy, maternal levels of both
factor VIII as well as vWF antigen increase
Because of this, pregnant women with vWD often
develop normal levels of factor VIII coagulant activity
as well as vWF antigen, Although the bleeding time
still may be prolonged.
If factor VIII activity is very low or if there is
bleeding, treatment is recommended. Desmopressin
by infusion may transiently increase factor VIII and
vWF factor levels.
Pregnancy outcomes in women with von Willebrand
disease are generally good, but postpartum
hemorrhage is encountered in up to 50 percent of
Patients with hemophilia A or B, because of prior
treatment with factor VIII or IX, may develop antibodies
directed against factor VIII or IX and may lead to life-
Rarely in puerperium, women resent as severe,
protracted, repetitive hemorrhage from the reproductive
tract starting a week or so after an apparently
The activated partial thromboplastin time is markedly
Treatment has included multiple transfusions of whole
blood and plasma and clotting factors.
-This disorder is a deficiency in Prothrombin, or Factor II, a
glycoprotein formed and stored in the liver.
-Some patients may show no symptoms, and others will suffer
-Patients may experience easy bruising, profuse nose bleeds,
postpartum hemorrhage, excessively prolonged or heavy
menstrual bleeding, and post-surgical hemorrhage.
-Hypo pro-thrombinemia may also be acquired rather than
inherited, and usually results from a Vitamin K deficiency
caused by liver diseases, newborn hemorrhagic disease, or
a number of other factors.
Thrombocytopenia is a reduction in platelet number below
1- Incidental thrombocytopenia of pregnancy
2- Increased consumption
3- Autoimmune thrombocytopenia (ITP)
5-Activated clotting mechanism
- HELP syndrome
6-Thrombotic thrombocytopenic purpura
7-Decreased platelet production (marrow suppression)
8- Malignant marrow infiltration
purpura (ITP) is a
disorder in which
Payne and colleagues
(1997) studies of
maternal ITP showed
that 12 percent of
newborns of ITP
patients had severe
-Major bleeding is rarely seen unless the platelet count is
-Maternal antibodies may cross the placenta and affect the
fetus , causing neonatal thrombocytopenia.
-four to ten percent of neonates are at risk of having sever
thrombocytopenia at birth or during the 1st
week of life.
FEATURES SUGGESTIVE OF
Platelet count < 100,000/mm3
Increased numbers of megakaryocytes
Increased platelet volume
• Corticosteriods – if platelet count <20,000/mm3 before
the onset of labor or < 50,000/mm3 at time of deliver
• High dose IV immunoglobulin produces increase in platelet
• Significant hemorrhage – immediate postpartum period
• The theoretical risk of intracranial haemorrhage in the
thrombocytopenic foetus has not been shown to be reduced
by C/S therefore C/S should be performed for obstetric
The acronym HELLP was coined by Weinstein in 1982 to
describe a syndrome consisting of Hemolysis, Elevated liver
enzymes and Low platelet count.
It is a syndrome that is characterized by hepatic endothelial
disruption followed by platelet activation, aggregation and
consumption, ultimately resulting in ischemia and hepatocyte
The findings of this multisystem disease are attributed to-
Abnormal vascular tone
1) Classical histological lesion in LIVER
HELLP Syndrome - 0.2 to 0.6% of all pregnancies.
In a multicenter study conducted on women with
HELLP syndrome 40 percent had adverse outcomes
such as subcapsular liver hematoma
,eclampsia,placental abruption, acute kidney injury,
and pulmonary edema,stroke, coagulopathy, acute
respiratory distress syndrome, and sepsis.
1) Immediate delivery - at or more than 34 weeks gestation.
2) Delivery within 48 hours after evaluation and stabilization of
the maternal clinical condition and Steroid treatment-27 to
34 weeks of gestation,
3) Expectant (conservative) management -before 27 weeks
PCV and FFP
ROLE OF TRANSFUSION
An acquired syndrome
Coagulation is always
the initial event
DIC is the most
complication with a
varying from 4-38%
Organ failure DEATHDEATH
Obstetric causes of DIC
Falls into three categories
conditions associated with release of tissue
thromboplastin that activates extrinsic pathway
- placental abruption
- dead foetus
- molar pregnancy
Conditions associated with endothelial damage
leading to activation of intrinsic & extrinsic pathways
- pre-eclampsia & eclampsia
Conditions having non-specific or indirect action
- amniotic fluid embolism
- gram negative septicaemia
- saline abortion
Clinical manifestations of
Those of the underlying cause
Those due to Complications of DIC
Involving skin & mucus membranes
Bleeding from the gum
Intracranial or intracerebral haemorrhage
Neurologic with multifocal lesions ,
delirium & coma
Dermatologic with focal ischemia &
Renal with cortical necrosis and uraemia
GIT acute ulceration with bleeding
Vascular occlusion causing pulmonary
infarction or peripheral vascular
Markedly decreased platelet count
Markedly Increased fibrin degradation products
Fragmented RBCs & microspherocytes in
peripheral blood film
Low fibrinogen , factor II , V & VII
Prolonged PT, PTT & TT
Microscopic findings in DIC
Paucity of platelets
๓ ธันวาคม ๒๕๕๑ T. TATU 65
Treatment of DIC
• Remove underlying cause
• Replenish depleted factors
• FFP Provides source of most factors
• Cryoprecipitate provides fibrinogen
• Platelet and blood support
• Cautious use of heparin
Is defined as a predisposition to thrombosis, secondary to any
persistent or identifiable hypercoagulable state.
Although these disorders are collectively present in about 15
percent of population, they are responsible for more than 50
percent of all thromboembolic events during pregnancy
DVT alone - more common antepartum whereas
pulmonary embolism - more common in the first 6 weeks
It can be inherited or acquired:
It should also be considered, in patients who have recurrent
pregnancy loss, unexplained IUFD's and early severe IUGR.
Causes of thrombophilia
1.Anti thrombin III deficiency:
-Anti thrombin III is a naturally occurring anticoagulant.
-It inactivate thrombin and factors IXa, Xa, XIa and XIIa.
-This is an autosomal-dominant condition.
-The clinical manifestation is thrombosis.
-The risk of thrombosis during pregnancy among antithrombin-
deficient women without a personal or family history is 3 to
7 percent, and it is 11 to 40 percent with such a history .
-It may be an acquired deficiency in patients who have DIC,
nephrotic syndrome, liver disease, pre-eclampsia, during
oral contraceptive use and during heparin therapy.
2. Protein C deficiency
-is also autosomal dominant
-This is the next thrombophilia.
3-Protein S deficiency is also autosomal dominant.
4-Factor V Leiden mutation.
5.Prothrombin gene mutation.
Acquired causes of thrombophilia - most common is
The antibodies are directed against cardiolipin(s) or
against phospholipid-binding proteins such as B2-
Women with moderate-to-high levels of these
antibodies may have antiphospholipid syndrome,
which is defined by a number of clinical features such
as thromboembolism or recurrent early trimester
unexplained fetal deaths.
It is found to be associated with 3.4% of early
It is postulated that they may interfere with the
normal function of phospholipids or phospholipid-
binding proteins involved in coagulation regulation,
including prothrombin, protein C, annexin V, and
tissue factor. Many of these antibodies are directed
against b2-glycoprotein I, which may itself function
as a natural anticoagulant
Blood coagulation is a major component of
haemostasis. Increased Coagulation factors
levels in pregnancy is meant to minimize blood
loss at time of delivery
This haemostatic mechanism could fail risking
Thrombocytopenic coagulation failure and DIC
syndrome are the most commonly seen in
Congenital causes of coagulation failure are
uncommon and usually already diagnosed prior
DIC syndrome is always secondary to an
If diagnosis of DIC is missed or appropriate
action is delayed it can cause serious
maternal morbidity or even death
Platelet transfusion and coagulation factor
replacement or fresh blood transfusion are
the main stay of treatment besides other
Use of heparin is controversial .
Haematologist opinion should be sought
before it’s use.
Robbins and Cotran 8th
Dacie and Lewis Practical Hematology 10th
Williams Obstetrics 23rd
it is certainly not unusual for women who have been
in clinical remission for several years to have
recurrent thrombocytopenia during pregnancy.
Although this may be from closer surveillance,
hyperestrogenemia has also been suggested as a
Platelet-associated IgG antibodies cross the placenta
and may cause thrombocytopenia in the fetus-
Payne and colleagues (1997) studies of maternal ITP
showed that 12 percent of newborns had severe