Septic shock and DIC
Septic shock and disseminated intravascular coagulation in obstetrics
Sepsis and haemorrhage are the leading causes of maternal death in Pakistan, and both meet in disseminated intravascular coagulation. Bacterial products trigger a cytokine storm that dilates vessels, makes capillaries leak and switches on clotting through tissue factor; obstetric events such as abruption pour tissue factor straight into the mother's blood. CPSP asks the toxins, mediators, organisms and the laboratory pattern of DIC.
From infection to shock
- Sepsis is life-threatening organ dysfunction caused by a dysregulated response to infection (SOFA rise of 2 or more). Septic shock needs vasopressors to keep MAP at 65 mmHg or more plus lactate above 2 mmol/L despite adequate fluids.
- Pregnancy normally raises the pulse by 10–15/min and white count to 12–15 × 10⁹/L, so general criteria mislead; obstetric early warning scores are used.
| Trigger | Source | Receptor and effect |
|---|---|---|
| Lipopolysaccharide (endotoxin), toxic part lipid A | Gram-negative outer membrane (E. coli, Klebsiella) | TLR4 with CD14 on macrophages; heat stable, cannot be made into a toxoid |
| Lipoteichoic acid | Gram-positive wall (Staphylococcus aureus) | TLR2 |
| Superantigens (streptococcal pyrogenic exotoxins, TSST-1) | Group A streptococcus, S. aureus | Bind MHC class II outside the groove and TCR Vβ, activating up to 20% of T cells: massive IL-2, TNF, IFN-γ |
- Exotoxins are proteins, specific and can become toxoids; endotoxin is LPS and cannot.
- Macrophages release TNF and IL-1, then IL-6, IL-8, platelet-activating factor and nitric oxide. LPS also activates factor XII, starting the intrinsic pathway and kallikrein, which makes bradykinin.
Why the patient is shocked
- Vasodilatation: cytokines induce inducible nitric oxide synthase (iNOS) in vascular smooth muscle; continuous NO raises cGMP and relaxes vessels, so hypotension resists fluids and catecholamines. Warm peripheries do not mean good perfusion.
- Capillary leak: the endothelial glycocalyx is shed, so crystalloid leaks out; vasopressors (noradrenaline) are started early.
- Impaired oxygen use: microcirculatory shunting and mitochondrial dysfunction give a high lactate with a high central venous oxygen saturation.
- Myocardial depression by TNF, IL-1 and NO can turn warm shock cold by day 3; it usually recovers.
- Relative adrenal insufficiency: low-dose hydrocortisone restores vascular response in vasopressor-dependent shock.
- Metabolic: stress hormones and cytokine insulin resistance cause hyperglycaemia; cytokines reduce canalicular bile export (conjugated jaundice with undilated ducts).
- Blood film: left shift, toxic granulation, Döhle bodies. Procalcitonin rises far more in bacterial than viral infection.
Obstetric sepsis
- Commonest sources: genital tract (endometritis after caesarean, septic abortion, chorioamnionitis) and urinary tract (pyelonephritis), the commonest source of Gram-negative septic shock.
- Puerperal sepsis is usually polymicrobial: anaerobic streptococci, Bacteroides, E. coli, group B streptococci, S. aureus. Group A streptococcus (Streptococcus pyogenes) is the most dangerous, killing within hours through superantigens.
- Clostridium perfringens after unsafe abortion: alpha toxin (lecithinase, phospholipase C) causes intravascular haemolysis with pink plasma, dark urine, bronze skin and gas in the uterus.
- Bacteroides fragilis forms abscesses through its capsular polysaccharide; most strains make β-lactamase.
- Chorioamnionitis triggers labour: cytokines induce COX-2 (PGE2, PGF2α) and metalloproteinases weaken membranes.
- Septic pelvic thrombophlebitis, usually of the right ovarian vein, causes fever persisting despite antibiotics that settles with heparin.
Disseminated intravascular coagulation
- The primary event is widespread activation of clotting, mainly through tissue factor exposed on monocytes and endothelium (sepsis) or entering the blood from decidua, placenta or amniotic fluid. Microthrombi consume platelets and factors, so bleeding follows from consumption.
- Secondary fibrinolysis makes fibrin degradation products, which inhibit fibrin polymerisation and platelet aggregation, worsening bleeding. D-dimer comes from plasmin digesting factor XIIIa cross-linked fibrin.
- In sepsis, cytokines reduce thrombomodulin (less activated protein C) and raise PAI-1, suppressing fibrinolysis, so organ thrombosis dominates; in abruption bleeding dominates.
- Fibrin strands in small vessels shear red cells into schistocytes (helmet cells). Microthrombi in kidney, lung and adrenals cause multi-organ failure and renal cortical necrosis.
| Test | DIC | Note in pregnancy |
|---|---|---|
| Platelets | Low | Gestational thrombocytopenia is mild |
| PT and APTT | Prolonged | Normal tests with schistocytes suggest TTP |
| Fibrinogen | Low | Normal at term is 4–6 g/L, so 2 g/L in PPH is already low |
| D-dimer and FDPs | High | D-dimer rises in normal pregnancy, so it is less specific |
Obstetric causes of DIC
| Cause | Mechanism |
|---|---|
| Placental abruption (especially concealed, fetal death) | Decidual tissue factor forced into maternal blood; fibrinogen falls within hours |
| Amniotic fluid embolism | Tissue factor in amniotic fluid; may present as coagulopathy alone |
| Retained dead fetus over 4 weeks | Slow leak of procoagulants: chronic low-grade DIC |
| Septic abortion, puerperal sepsis | Cytokine-induced tissue factor |
| Severe pre-eclampsia, HELLP, acute fatty liver | Endothelial injury, liver failure |
| Massive PPH | Dilution and consumption |
- Treat the cause (deliver the placenta, control the source of sepsis); support with FFP (all factors), cryoprecipitate (fibrinogen, VIII, von Willebrand factor) and platelets.
Remember In DIC clotting comes first; bleeding is the result of consumption.
Exam trap A fibrinogen that is normal for a non-pregnant woman may be dangerously low at term.
Exam trap Septic shock with warm peripheries is NO-driven vasodilatation, and a high ScvO2 does not mean tissues are well oxygenated.
Test yourself on this topic
5 of the 45 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
A woman at 35 weeks has a concealed placental abruption with a dead fetus. Within hours her fibrinogen is 0.9 g/L and she oozes from venepuncture sites. What is the main trigger of her coagulopathy?
Answer: Placental and decidual tissue factor entering her blood
The decidua and placenta are rich in tissue factor (thromboplastin). In abruption, the retroplacental clot forces this material into the maternal circulation, activating coagulation widely and consuming fibrinogen, factors and platelets; fibrinolysis then adds fibrin degradation products. Abruption with fetal death is the commonest obstetric cause of acute DIC. Blood loss and dilution worsen it but do not explain such a rapid fall in fibrinogen.
Abruption and DIC
- Decidua rich in tissue factor
- Forced into maternal blood
- Rapid fall in fibrinogen
- Worst with fetal death
Remember Abruption pumps thromboplastin into the mother.
Exam trap Concealed abruption can cause DIC with little visible vaginal bleeding.
Why the other options are wrong
- Loss of clotting factors in the concealed haemorrhage alone Clot consumption adds to it, but systemic activation is the main cause.
- Dilution from crystalloid infusion No large infusion is described.
- Liver failure from shock Not the cause of such rapid onset.
- Vitamin K deficiency Not relevant acutely.
A woman with septic shock after a septic miscarriage remains hypotensive after 3 litres of IV fluid, needing noradrenaline. Which enzyme, expressed in vascular smooth muscle in response to endotoxin and cytokines, is chiefly responsible for her loss of vascular tone?
Answer: Inducible nitric oxide synthase
Lipopolysaccharide, TNF and IL-1 induce the inducible isoform of nitric oxide synthase (iNOS) in vascular smooth muscle and macrophages. Unlike the constitutive endothelial enzyme, iNOS produces large amounts of nitric oxide continuously, activating guanylyl cyclase and raising cGMP, which relaxes vascular smooth muscle. This causes profound, catecholamine-resistant vasodilation. COX-1 is a constitutive enzyme and ACE and endothelin-converting enzyme produce vasoconstrictors.
NO in septic shock
- LPS, TNF, IL-1 induce iNOS
- Large, continuous NO output
- cGMP: smooth muscle relaxation
- Vasopressor-resistant hypotension
Remember Septic vasoplegia is driven by inducible NO synthase.
Exam trap Endothelial NOS (eNOS) is constitutive and makes small amounts of NO.
Why the other options are wrong
- Cyclo-oxygenase-1 Constitutive; not induced in sepsis.
- Angiotensin-converting enzyme Produces angiotensin II, a vasoconstrictor.
- Endothelin-converting enzyme Produces endothelin, a vasoconstrictor.
- Phospholipase A2 Upstream of eicosanoids, not the main cause of vasoplegia.
A woman with DIC after abruption is bleeding from the uterus and drip sites. Her PT ratio is 1.9 and APTT ratio 1.8, with fibrinogen 1.8 g/L and platelets 70 × 10⁹/L. Which blood component best replaces the full range of consumed clotting factors?
Answer: Fresh frozen plasma
Fresh frozen plasma contains all the plasma clotting factors, including the labile factors V and VIII, as well as fibrinogen and the natural anticoagulants. It corrects prolonged PT and APTT in a bleeding patient with consumptive coagulopathy. Cryoprecipitate is a more concentrated source of fibrinogen, factor VIII and von Willebrand factor, used when fibrinogen is very low. Platelets correct thrombocytopenia only, and vitamin K takes hours and does not replace consumed factors.
Products in DIC
- FFP: all clotting factors
- Cryoprecipitate: fibrinogen, VIII, vWF
- Platelets if low and bleeding
- Treat the cause: deliver the placenta
Remember Prolonged PT and APTT while bleeding: give FFP.
Exam trap Products support the patient; only removing the cause stops DIC.
Why the other options are wrong
- Platelet concentrate Corrects the platelet count only.
- Packed red cells Replace oxygen-carrying capacity, not factors.
- Albumin 20% Contains no clotting factors.
- Vitamin K injection Too slow; does not replace consumed factors.
Two women in the postnatal ward have fever and raised CRP. One has influenza and the other has early Gram-negative sepsis from an infected caesarean wound. Which blood marker rises much more in the bacterial infection and helps tell them apart?
Answer: Procalcitonin
Procalcitonin, the precursor of calcitonin, is normally made only in thyroid C cells. In bacterial sepsis, endotoxin and cytokines such as IL-6 and TNF switch on its production in many tissues, including liver, lung and fat, and levels rise within hours. Interferon-γ released in viral infection suppresses this response, so procalcitonin stays low in most viral illnesses. Calcitonin itself does not rise. ESR and ferritin rise in many inflammatory states.
Procalcitonin
- Calcitonin precursor
- Made in many tissues in bacterial sepsis
- Suppressed by interferon-γ (viral)
- Rises within hours
Remember Procalcitonin flags bacteria, not viruses.
Exam trap Procalcitonin can also rise after major surgery, trauma and burns without infection.
Why the other options are wrong
- Erythrocyte sedimentation rate Non-specific and raised in pregnancy.
- Ferritin An acute-phase reactant; not specific.
- Lymphocyte count Falls in many severe infections; not discriminating.
- Calcitonin Mature calcitonin does not rise in sepsis.
In septic women who develop DIC, TNF and IL-1 not only increase clotting but also weaken the protein C anticoagulant system. Which endothelial change is chiefly responsible?
Answer: Reduced endothelial thrombomodulin
Protein C is activated when thrombin binds thrombomodulin on endothelial cells. Activated protein C, with protein S, inactivates factors Va and VIIIa. Inflammatory cytokines down-regulate endothelial thrombomodulin and the endothelial protein C receptor, so less protein C is activated and thrombin generation goes unchecked. Prostacyclin, tPA and heparan sulphate are anticoagulant, so an increase in them would oppose thrombosis.
Protein C in sepsis
- Thrombin + thrombomodulin activates protein C
- APC inactivates Va and VIIIa
- Cytokines down-regulate thrombomodulin
- Less APC: more thrombin
Remember Sepsis switches off the protein C brake.
Exam trap Sepsis also raises PAI-1, so fibrinolysis is suppressed early in septic DIC.
Why the other options are wrong
- Increased endothelial prostacyclin Would reduce, not promote, thrombosis.
- Increased tissue plasminogen activator Would increase fibrinolysis; in sepsis PAI-1 rises instead.
- Increased heparan sulphate on endothelium Would enhance antithrombin; it is actually reduced.
- Loss of von Willebrand factor Not the mechanism.
Where this sits in the CPSP syllabus
- Obstetrics & Gynaecology, Paper 2: General pathology in obstetrics, Septic shock and disseminated intravascular coagulation
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