DIC vs TTP vs HUS: mechanism and the PT/PTT
DIC vs TTP vs HUS: schistocytes and a low platelet count can appear in all three. What separates disseminated intravascular coagulation, TTP and HUS is what forms the clot, and that decides the labs.
Chapters (9)
Distinguish DIC, TTP and HUS by mechanism (consumptive coagulation, ADAMTS13 deficiency or toxin-mediated endothelial injury) and by the PT and PTT.
The short version
- DIC, TTP and HUS all form small clots in small vessels and consume platelets; red cells shearing into schistocytes is defining in TTP and HUS and can also occur in DIC.
- DIC is consumption: the PT and PTT are typically prolonged and fibrinogen low.
- TTP is ADAMTS13 activity below 10 percent with a normal PT and PTT, treated with plasma exchange and immunosuppression.
- HUS is endothelial injury, usually from Shiga toxin, with kidney failure and a normal ADAMTS13 activity.
DIC vs TTP vs HUS: one blood film, three diseases
Picture three patients with the same blood film: fragmented red cells and very few platelets. One is confused, one is in kidney failure, and one is oozing from every puncture site. The film cannot tell you which disease each has.
This lesson separates DIC vs TTP vs HUS by mechanism, and by the PT and PTT. In all three, small clots form inside small vessels. Platelets are used up, and red cells shear apart as they squeeze past the strands, giving schistocytes.[1][4][8]
What differs is what forms the clot, and that decides the labs.
So the order of thinking is simple: first the mechanism, then the PT and PTT. DIC is a problem of the cascade. TTP is a problem of von Willebrand factor and platelets. HUS is a problem of the endothelium.
DIC: the clotting cascade itself runs out of control
In disseminated intravascular coagulation (DIC), a trigger such as sepsis, trauma, cancer or an obstetric catastrophe drives tissue factor and thrombin generation.[1][3]
Fibrin microthrombi form, while platelets and clotting factors are consumed. The patient both clots and bleeds.[1][2]
- PT and PTT prolonged
- Fibrinogen low
- D-dimer high
- Platelets low
The labs typically show this pattern.[1][4] Treatment is to fix the underlying cause.[2][1]
TTP: the cascade is intact, the platelets are the problem
In thrombotic thrombocytopenic purpura (TTP), an enzyme, ADAMTS13, normally trims von Willebrand factor. When its activity falls below 10 percent, usually from an autoantibody, ultralarge von Willebrand multimers build up and grab platelets, forming platelet-rich microthrombi.[5][4][6]
The classic pentad, though few patients show all five, is fever, thrombocytopenia, haemolytic anaemia, renal injury and neurological signs.[5]
The PT and PTT are normal, because the cascade is untouched.[4][7]
Untreated, TTP is often fatal, so plasma exchange and immunosuppression start on suspicion.[5][4]
HUS: the target is the endothelium
In haemolytic uraemic syndrome (HUS), the classic cause is Shiga toxin from E. coli, after bloody diarrhoea.[8][10]
The toxin binds the receptor Gb3 on endothelial cells and inactivates ribosomes. The injured wall promotes platelet clots, and the kidney suffers most.[8][9]
The triad is thrombocytopenia, haemolytic anaemia with schistocytes, and acute kidney injury. ADAMTS13 activity and the PT and PTT are normal.[8][7][4]
DIC, TTP and HUS compared: mechanism and PT/PTT
| DIC | TTP | HUS | |
|---|---|---|---|
| What forms the clot | The clotting cascade runs out of control | Ultralarge VWF multimers and platelets | Injured endothelium (usually Shiga toxin) |
| PT and PTT | Prolonged | Normal | Normal |
| Fibrinogen and D-dimer | Fibrinogen low, D-dimer high | Not the defining feature | Not the defining feature |
| ADAMTS13 activity | Not the defining feature | Below 10 percent | Normal |
| Treatment | Fix the underlying cause | Plasma exchange and immunosuppression | Supportive, with dialysis when needed |
- Look at the PT, PTT and fibrinogenIn DIC the cascade is consumed, so the PT, PTT and fibrinogen are typically abnormal. In TTP and HUS the cascade is untouched and the PT and PTT are normal.[4][7]
- Check ADAMTS13 activityBelow 10 percent is TTP, treated with plasma exchange and immunosuppression. Normal activity points to HUS.[5][7]
- Look for the Shiga toxin storyBloody diarrhoea and a toxin-producing E. coli suggest the typical form of HUS. Without Shiga toxin, atypical HUS from complement dysregulation is the alternative.[8][10]
Worked example: a TTP case
A 28-year-old woman has fever and confusion, schistocytes, and a low platelet count. Her PT and PTT are normal, and her ADAMTS13 activity is 3 percent.
- Schistocytes and a low platelet count: a microangiopathic picture, not yet a diagnosis
- PT and PTT normal: the cascade is untouched, so not DIC
- ADAMTS13 activity 3 percent, below 10 percent: TTP
- Plasma exchange and immunosuppression
Practice question
Original · USMLE styleA 2-year-old boy is brought to the emergency department with pallor, lethargy and markedly reduced urine output. He had 3 days of bloody diarrhoea that started 6 days ago. Laboratory studies show:
| Haemoglobin | 7.9 g/dL |
|---|---|
| Platelet count | 48 × 10⁹/L |
| Serum creatinine | 3.1 mg/dL |
| Prothrombin time, activated partial thromboplastin time, fibrinogen | Within reference ranges |
| ADAMTS13 activity | Within reference range |
| Stool Shiga toxin PCR | Positive |
Common questions
How do you tell DIC from TTP?
By the PT, PTT and fibrinogen. In DIC the PT and PTT are prolonged and fibrinogen is low, because the cascade is consumed. In TTP the PT and PTT are normal, because the cascade is untouched.
How do you tell TTP from HUS?
By ADAMTS13 activity and the cause. TTP has ADAMTS13 activity below 10 percent, usually from an autoantibody. HUS has normal ADAMTS13 activity and is usually caused by Shiga toxin after bloody diarrhoea.
Why do DIC, TTP and HUS all show schistocytes?
In all three, small clots form inside small vessels, and red cells shear apart as they squeeze past the strands. Schistocytes define TTP and HUS and are often, but not always, seen in DIC.
What is atypical HUS?
Atypical HUS has no Shiga toxin. It comes from complement dysregulation.
Transcript
Read the full narration, by chapter593 words
0:00The case: three patients, the same blood film
Three patients, one blood film: fragmented red cells and very few platelets. One is confused. One is in kidney failure. One is oozing from every puncture site. Same film, three different diseases. How do we separate them? Today: tell DIC, TTP and HUS apart by mechanism, and by the PT and PTT.
0:25Small-vessel clots, platelet consumption and schistocytes
In all three, small clots form inside small vessels. Platelets are used up, and red cells shear apart as they squeeze past the strands, giving schistocytes. What differs is what forms the clot, and that decides the labs. In DIC, the clotting cascade itself runs
0:42DIC: the cascade runs away, PT and PTT go up, fibrinogen falls
out of control. A trigger such as sepsis, trauma, cancer or an obstetric catastrophe drives tissue factor and thrombin generation. Fibrin microthrombi form, while platelets and clotting factors are consumed, so the patient both clots and bleeds. The labs typically show it: PT and PTT prolonged, fibrinogen low, D-dimer high, platelets low. Treatment is to fix the underlying cause. In TTP, the cascade is intact;
1:16TTP: ADAMTS13 below 10 percent, ultralarge VWF, normal PT and PTT
the platelets are the problem. An enzyme, ADAMTS13, normally trims von Willebrand factor. When its activity falls below 10%, usually from an autoantibody, ultralarge von Willebrand multimers build up and grab platelets, forming platelet-rich microthrombi. The classic pentad, though few patients show all five, is fever, thrombocytopenia, haemolytic anaemia, renal injury and neurological signs. The PT and PTT are normal, because the cascade is untouched. Untreated, TTP is often fatal, so plasma exchange and immunosuppression start on suspicion. In HUS, the target is the endothelium.
2:03HUS: Shiga toxin, Gb3, endothelial injury, normal ADAMTS13
The classic cause is Shiga toxin from E coli, after bloody diarrhoea. The toxin binds the receptor Gb3 on endothelial cells and inactivates ribosomes. The injured wall promotes platelet clots, and the kidney suffers most. The triad: thrombocytopenia, haemolytic anaemia with schistocytes, and acute kidney injury. ADAMTS13 activity and the PT and PTT are normal. Care is supportive, with dialysis when needed. Atypical HUS has no Shiga toxin; it comes from complement dysregulation. An example: a 28-year-old woman
2:46Worked example: 28-year-old with ADAMTS13 at 3 percent
has fever and confusion, schistocytes, and a low platelet count. Her PT and PTT are normal, and ADAMTS13 activity is 3%. Below 10%: TTP. Plasma exchange and immunosuppression.
3:05Your turn: a practice question
Your turn. A 2-year-old boy has had 3 days of bloody diarrhoea, which began 6 days ago. He is now pale, lethargic, and passing little urine. Haemoglobin is 7.9, platelets 48, and creatinine 3.1. The smear shows schistocytes. PT, PTT and fibrinogen are normal, and ADAMTS13 activity is normal. Stool testing is positive for Shiga toxin genes. Which of the following best explains his condition? A, systemic thrombin generation with consumption of clotting factors. B, autoantibody against ADAMTS13 with ultralarge multimers. C, Shiga toxin injury to glomerular endothelial cells. D, inherited dysregulation of the alternative complement pathway. E, autoantibody against platelet glycoprotein IIb/IIIa. Pause here and decide.
4:08The answer, one option at a time
A is out: DIC would prolong the PT and PTT and lower the fibrinogen. B is out: that is TTP, and his ADAMTS13 activity is normal. D is out: atypical HUS is complement-driven and has no Shiga toxin, and his stool is positive for the toxin. E is out: immune thrombocytopenia gives isolated low platelets, with no schistocytes, anaemia or kidney injury. So the answer is C. Bloody diarrhoea, toxin-positive stool, the triad, normal clotting and ADAMTS13: Shiga toxin HUS.
4:57Recap pocket card and what comes next
Three things to keep. One: DIC is consumption, so the PT, PTT and fibrinogen are abnormal. Two: TTP is ADAMTS13 below 10%, with normal PT and PTT, treated with plasma exchange and immunosuppression. Three: HUS is endothelial injury, usually Shiga toxin, with kidney failure and a normal ADAMTS13. Next, leukaemia: myeloid versus lymphoid.
Sources
Numbers in the text, e.g. [1], point here- LITFL. Disseminated intravascular coagulation. litfl.com/disseminated-intravascular-coagulation/
- J Intensive Care 2014, DIC treatment. europepmc.org/article/PMC/PMC4267589
- Sepsis-associated DIC, 2023. europepmc.org/article/PMC/PMC10202753
- Int J Lab Hematol 2022, thrombotic microangiopathies. europepmc.org/article/PMC/PMC9544907
- J Clin Med 2021, thrombotic thrombocytopenic purpura. europepmc.org/article/PMC/PMC7867179
- Res Pract Thromb Haemost 2019, TTP: toward targeted therapy. europepmc.org/article/PMC/PMC6332733
- Crit Care 2018, thrombocytopenia in the ICU: DIC and thrombotic microangiopathies. europepmc.org/article/PMC/PMC5998546
- Toxins 2020, STEC-HUS narrative review. europepmc.org/article/PMC/PMC7076748
- Toxins 2012, Shiga toxins and the pathophysiology of HUS. europepmc.org/article/PMC/PMC3509707
- Semin Nephrol 2013, atypical HUS. europepmc.org/article/PMC/PMC3863953
- J Clin Med 2021, immune thrombocytopenia. europepmc.org/article/PMC/PMC7920457
- Further sources are in the lesson ledger.
The practice question is original and its patient is synthetic. Every fact is checked against the sources above in independent accuracy reviews. Always follow your local guidelines and your own laboratory’s ranges.
Image credits. Illustrations: Servier Medical Art (smart.servier.com), CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/), adapted (recoloured, outlined, resized): brain, glomerulus, blood vessel, thrombus, blood bag (recoloured as plasma), intestine. Red blood cell, platelet and von Willebrand factor: NIAID NIH BioArt Source (public domain). Bandage, oncology, pregnancy and E. coli icons: Health Icons / Bioicons (CC0). The tube, fibrin, scissors, gauge, slips, cards and all handwriting are drawn in code (original). No AI-generated teaching images.
Corrections. None so far. Spotted an error? Email info@medservatory.com with the lesson code MS-S1-HEME-012.
For exam study only, not medical advice. Read the medical disclaimer.
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