Disseminated intravascular coagulation (DIC)

كلية الطب ? جامعة بابل المرحلة الرابعة
د-نسرين مالك
obstetrics

disseminated intravascular coagulation (dic)
is a systemic process producing both thrombosis and hemorrhage.it is not clinical entity, always it consider secondary phenomena(i.e as complication of underlying pathological process against which treatment should be directed).
it is of two types:-
i-consumptional:-which is initiated by a number of defined disorders and consists of the following components:
1-exposure of blood to procoagulants such as tissue factor and cancer procoagulant.
2-formation of fibrin within the circulation .
3-fibrinolysis.
4-depletion of clotting factors.
5-end-organ damage.


pathophysiology of the clinical manifestations of disseminated intravascular coagulation


ii-dilutional type:-this occur when massive blood loss is replaced by crystalloid solution and packed rbc this will lead to depletion of platelates and clotting factors. dilutional coagulopathy and impaired haemostasis mostly related to thrombpcytopenia.




major causes of disseminated intravascular coagulation

a-events that initiate dic:-
1 complications of pregnancy.
amniotic fluid embolism.
abruptio placentae.
hellp syndrome.
eclampsia and severe preeclampsia.
retained dead fetus.
septic abortion.
hydatidiform mole.

2-septicemia :- gram negative and gram positive
3-crush injury or complicated surgery
4-severe head injury
5-cancer procoagulant (trousseau s syndrome)
6-acute leukemia.
7-others.

b-events that complicate and propagate dic:-
1-shock
2-complement pathway activation.

clinical presentation and lab diagnosis,of dic :-
there is grate spectrum of manifestations of dic ,and the severity of the condition may progress to more advanced stages if no appropriate measures is taken.
1- stage i ( low grade dic ) ,( compensated):-this stage is seen in
• preeclampsia
• retained dead fetus.

usually it dose not give rise to any clinical manifestations, but may be hazardous to the mother and fetus as significant bleeding may occur if there is any bruise , or at time of placental separation.

in vitro findings includes the following:-
1- increased fibrinogen degradation products( fdps ? ).
2- increased soluble fibrin complexes( this consist from fibrinogen and fibrin dimmers ).
3- increased ratio of vwf to factor viiic.
4- normal plasma fibrinogen and platelet count, and normal haemostasis fuction test(aptt, pt,tt) .

2- stage ii( uncompensated but no haemostatic failure):- this stage is seen in

• small abruptio .
• severe preeclampsia

also with no clinical manifestations, but more increase in risk for bleeding if bruising occur or at time of placental separation.

in vitro findings includes the following:-
as findings of stage i ( low grade dic ) plus:-
1-decrease fibrinogen and platelet count.
2- decrease factors v and viii.
3- prolongation of haemostasis fuction test (aptt, pt,tt) .
4-blood film shows microangiopathic hemolytic anemia, in which there is fragmentation and destruction of rbc when squeeze through intravascular fibrin strands.

3-stage iii (rampant with haemostatic failure):- this stage is seen in

• abruptio placenta.
• amniotic fluid embolism.
• eclampsia.

the clinical presentation of this stage is :-
1-coagulation defect which lead to:-
a-catastrophic, excessive bleeding at site of modest trauma.
b-spontaneous bleeding from the gum and nose.
2-thrombocytopenia:- which presented with purpuric spotes at pressure sites.

the fate of above two points is hypovolemic shock which is fatal, also there will be circulatory destruction leading to tissue hypoperfusion , ischemia, and necrosis , which will end up in organ failure, this started by irreversible cortical necrosis of the kidney followed by other organs such as respiratory system leading to ards.
in vitro findings includes the following:-
1-sever platelets depletion.
2-gross depletion of coagulation factors particularly fibrinogen.
3- ( fdps ?? ).
4- prolongation of haemostasis fuction test(aptt, pt,tt) .

treatment of dic:-
dic is a serious complication associated with a high mortality rate, determined in part by the underlying disease, so the treatment include:-
1-correction of hypovolemia if present by approperate replacement .
2-treatment of haemostatic failure, the integrity of haemostatic system should be checked by aptt, pt,tt.
3-correction of the underlying disease and initiating factors in any patient with dic.

management of hypovolemic shock is the same in all conditions , firstly there is no urgent
need to especify the deficient coagulation factor.
more than one intravenous line is required to maintain adequate replacement, and foley’s catheter inserted to the bladder to monitor renal perfusion (30 ml\hr to ensure acceptable renal perfusion). central venous pressure line insertion is delayed to after coagulation defect corrected.
we should restore circulation without any delay, to avoid renal shut down , because when circulation restored the fdps will be cleared from the circulation effectively by the reticuloendothelial system (res) which will be stimulated to synthesize normal procoagulant and clotting factors.

the replacement therapy:-
for correction of hypovolemia and haemostatic failure, there is five major components :-
1-plasma substitutes.
2-plasma components.
3-whole blood
4-packed red blood cells.
5-platelet concentrate.

1-plasma substitutes:-
a-simple crystalloid:-(hartman’s or riner lactate) we need to transfuse 2-3 times the volume of estimated blood loss because the crystalloid remains in circulation for a short time. this substitutes are used as a gap stopper until blood is prepared which needs 20-40 minutes to maintain renal function..

b- artificial colloids:-include:-
1-dextrans:-are adversely affect platelet function, may cause pseudoagglutination and interfere with the interpretation of subsequent blood grouping, and cross matching tests. dextrans are also associated with allergic anaphylactoid reactions probably related to igg and igm anti dextran antibodies , therefore they are better avoided.
2-hydroxyethyl starch( hetastarch):- anaphylactoid reactions have occurred use with caution in patients allergic to corn (may have cross allergy to hetastarch) may interfere with platelet function large volume may cause dropings in hemoglobin concentrations it use with caution in patients at risk from overexpansion of blood volume, including the very young or aged patients, those with chf or pulmonary edema volumes >1500 ml may interfere with platelet function and prolong pt and ptt times also use it with caution in patients with history of liver disease.
3- gelatin solutions:-are of three types:-
haemacele: none immunogenic with long half life and dose not interfere with cross match or platelet function, so it plays an important role in the resuscitation of the patient until blood is prepared, it is commonly used as first line agent in correction of hypovolemia.
human albumin preparation(albuminoids):-this has adverse effect on the heart, lung, impair hemostasis , and may cause anaphylaxis and fever , so it is not used.
purified protein fraction:-this type of colloid has no risk of infection.

2-plasma components:-
a-fresh frozen plasma(ffp):- ffp is a potent plasma expander ,is prepared from separated plasma from whole blood after 6 h of donation and frozen rapidly at – 30 c?, and is effective up to one year.
each bag contains 250 ml which containing all coagulation factors in plasma(ii, v, vii, ix, xi), and antithrombin iii .
we have to give 2 units of ffp for every 4-6 units of packed rbc, and 4 units for each 6 units of whole blood to avoid dilutional coagulopathy.
indications of ffp:- 1-acute treatment of consumptional and dilutional dic.
2-bleeding female with prolonged tt, pt, aptt.
3-when fibrinogen level is less than 100 mg\dl.
the dose of ffp is 10-15 ml\kg body weight.
one unit of ffp (250 ml ) increase each clotting factors 2-3? .
b-cryoprecipitate:-is prepared from ffp, unit contains 50 ml which containing factors viiic, viiivwf, fibrinogen 150 mg, xiii, and fibronectin , but luck antithrombin iii.
cryoprecipitate increase risk of infection.
indications of cryoprecipitate:-
1-specific factor deficiency especially fibrinogen(because it is richer in fibrinogen than ffp) so given if plasma fibrinogen level is less than100 mg\dl.
2-pateint with volume over loud like in heart failure.

the dose of cryoprecipitate is 1 unit for each 5 kg of body weight.
one unit of cryoprecipitate will increase fibrinogen 10 mg\dl.

3-whole blood:-
the fresh blood is no longer available because adequate viral screening (hbv, hiv, cmv, ebv), and abo, rh grouping required at least 18-24 hours , and any transfusion earlier than this time will increase the risk of incompatibility and viral infection.

giving old blood is a serious wastage of vitally needed components which frequently required for patient with specific deficiency, because old blood even when optimally stored at 4 c? will lose platelets function in 4 days , and factors v, viii in the first 24 hours, and the rest of haemostatic components lost in 72 hours.
whole blood given when blood loss exceed 25? of total blood volume. one unit of whole blood increase hb 1g\dl.

4-packed red blood cells:-one unit of packed red blood cells contains 250 ml which provide hematocrit concentration of about 60-70?,and this elevate haematocrit of the patient by 3-4?.

indications of packed red blood cells:-
1-pateint with volume over loud.
2-used in case of acute blood loss especially in patient with pcv 21?, and hb 7mg\dl.

packed red blood cells and ffp when given together will provide all fresh blood components except platelets so they are alternatives for fresh blood transfusion.


5-platelet concentrate:-it prepared from whole blood by centrifugation , and can not stored more than 4 days. one unit contains 50 ml. during transfusion the leukocytes filter should not use. each unit contains 0.5 ml of rbc, so anti d should be given (one dose every 15 ml of rbc).

indications of platelet concentrate:-
1- indicated in patients with marked thrombocytopenia (<20,000/microl) or moderate thrombocytopenia (<50,000/microl) with serious bleeding or for surgical schedules.
2-indicated in case of abnormal platelet function which diagnosed when platelet count is normal and bleeding time more than 9 minutes.

the dose of platelet concentrate is 1 unit \10 kg of body weight \day, (minimum of 6 units\day).
one unit of platelet concentrate increase platelet count by 5000- 10,000\ microl.
role of drugs in treatment of dic:-

1- heparin:- there is arguments against the routine use of heparin include potential aggravation of bleeding and the likelihood that it will have reduced effect due to the low levels of antithrombine . the administration of heparin is generally limited to the subset of patients with chronic, compensated dic who have predominantly thrombotic manifestations. it is important to be sure that the patient s antithrombin (at) level is near normal (ie, 80 to 100 percent) in order for heparin to be effective.

2- epsilon (amino caproic acid) :- it decreases fibrinolysis by inhibiting plasmin so, it preserves fibrin clots , but if fibrin clots not cleared from microcirculation this will lead to obstruction of small blood vessels then organ failure will occur so, it is better avoided.

recently there are many studies done to prevent the development of dic by giving treatment to inhibit or reduce the production of tissue factors that predispose to dic.

coagulation and fibrinolytic systems during pregnancy:-

pregnancy effects on coagulation factors detected from 3rd month of gestation, there is change in balance between procoagulant and anticoagulant factors resulting in increase coagulation and decrease of fibrinolysis due to the following:-.

1- there is increase in coagulation activity due to increase of procoagulant factors ( vii increase 10 fold ,viii doubled "both vwf and viiic increase progressively" , ix, x, xii, and increase fibrinogen by 50? from 2.5 to 4 - 6 mg\dl.
2- decrease in factors xi, xiii.
3- decrease anticoagulant (antithrombin iii , protein c, activated protein c are unchanged, while factor s is reduced).
4- the reduction of fibrinolysis during pregnancy is resulting from the effect of plasminogen activator inhibitor type ii.
5- no effect on platelet count or life spine during pregnancy.

coagulation and fibrinolytic systems during puerperium:-

following delivery of the placenta there is:-
1-increase plasminogen activator gradually.
2-increase fibrinogen.
3-increase of platelet count.

there is increase risk of thrombosis within 4-6 week after delivery.