75 yo male presents with increasing shortness of breath, general deterioration over 6 weeks and vague history of melena.
Past Medical History includes ischaemic heart disease managed conservatively and congestive heart failure.
Current Medication: aspirin, dabigatran, rabeprazole, ramipril (all taken morning of admission)
Examination on admission P 145, systolic BP 90, O^2 sats 88% and crackles on examination of the chest. Abdominal examination demonstrated some mild epigastric tenderness.
Blood results :
| Parameter | Patient | Normal Range |
|---|---|---|
| Haemoglobin (g/L) | 76 | 135-180 |
| White Cell Count (x10^9/L) | 14.3 | 4-11 |
| Platelets (x10^9/L) | 382 | 150-400 |
| MCV | 74 | 80-100 |
| Prothrombin (s) | 52.9 | 12-16.5 |
| INR | 3.9 | 0.9-1.3 |
| APTT (s) | 87.6 | 27.5-38.5 |
| Fibrinogen (g/L) | 4.1 | 2-4 |
| APTT (50:50) (s) | 58 | 27.5-38.5 |
| Creatinine (umol/L) | 161 | 60-110 |
What are your concerns and next steps?
An urgent Dabigatran level was obtained. It was 556ng/mL.
Idarucizumab was given.
Blood tests 4 hrs later revealed:
| Parameter | Patient | Normal Range |
|---|---|---|
| Haemoglobin (g/L) | 78 | 135-180 |
| White Cell Count (x10^9/L) | 16.5 | 4-11 |
| Platelets (x10^9/L) | 379 | 150-400 |
| Prothrombin (s) | 23.3 | 12-16.5 |
| INR | 1.6 | 0.9-1.3 |
| APTT (s) | 34.4 | 27.5-38.5 |
| Fibrinogen (g/L) | 4.4 | 2-4 |
| Creatinine (umol/L) | 177 | 60-110 |
Can you interprete these results?
Repeat blood tests 24 hrs later:
| Parameter | Patient | Normal Range |
|---|---|---|
| Prothrombin (s) | 36.2 | 12-16.5 |
| INR | 2.6 | 0.9-1.3 |
| APTT (s) | 55.4 | 27.5-38.5 |
| Fibrinogen (g/L) | 5.3 | 2-4 |
| APTT (50:50) (s) | 36.8 | 27.5-38.5 |
| Creatinine (umol/L) | 154 | 60-110 |
| Bilirubin (umol/L) | 50 | <20 |
| ALT (U/L) | 1360 | <40 |
| ALP (U/L) | 104 | 30-110 |
| GGT (U/L) | 45 | <60 |
| Alb (g/L) | 30 | 35-50 |
Should this patient have another dose of Idarucizumab?
This patient has presented with microcytic anaemia and a history of bleeding. He now sounds like he is in shock with tachycardia and hypotension. He is also hypoxic.
The blood count suggests that he likely has a reactive leucocytosis and his platelet count is normal. The microcytic anemia is likely due to iron deficiency given the history however iron stores are not provided. This should be ordered.
He is coagulopathic with a raised PT and APTT. The APTT does not correct with 50:50 mix suggesting the presence of an inhibitor. It is noted he is on dabigatran which can cause this picture. He has renal impairment which can delay the excretion of dabigatran exaccerbating its effect.
A dabigatran level should be ordered along with LFT and d dimer. He needs to be clinically resuscitated and consideration of Idarucizumab should be made.
The level of Dabigatran suggests that there is still a significant effect of the drug on coagulation. Idarucizumab was rightly given. It is a humanised monoclonal Ab fragment that binds free and thrombin bound Dabigatran and neutralises its effect. Immediately after its infusion, the plasma level of Dabigatran falls by ~99%. The majority of people will have sustained effect for up to 12hrs however some will have diminished effect due to the redistribution of Dabigatran back into the circulation from the periphery.
Blood tests after 4 hrs show a normalisation of the APTT which is very sensitive to Dabigatran. The PT is still slightly prolonged suggesting another pathology.
Blood results 24 hours later showed a prolonged PT and APTT however the APTT corrects into the normal range with 50:50 mix. Fibrinogen is slightly elevated. His creatinine is slightly better however his liver function tests have deteriorated with a picture consistent with ischaemic liver injury.
He should not need another dose of idarucizumab as the APTT is correcting suggesting that the coagulopathy is not consistent with the effect of dabigatran. Instead, it seems more likely related to coagulopathy related to acute liver injury which was sustained during the hypotensive episode. If the patient is symptomatically bleeding, the coagulopathy can be corrected with FFP. Prothrombinex concentrate would be less ideal as it does not contain any natural anticoagulants and may indeed contribute to a prothrombotic tendency.