Diagnostic Assessment — Vaccine-Induced Thrombotic Thrombocytopenia
Example 1 of 1 · fictitious patient (Veteran DR)
Diagnostic Assessment
Vaccine-Induced Thrombotic Thrombocytopenia
BOP Code: 34 of 2022 (Vaccine-Induced Thrombotic Thrombocytopaenia)
RH Code: 33 of 2022 (Vaccine-Induced Thrombotic Thrombocytopaenia)
ADF History
Veteran DR, date of birth 19 July 1974, Royal Australian Air Force, Aircraft Technician (Flight Sergeant), enlisted 06 September 1993, medically discharged 30 September 2022. Operational service: East Timor, 25 September 1999 to 20 February 2000 (warlike); Middle East Area of Operations, 12 January 2005 to 15 July 2005 (warlike); Middle East Area of Operations, 01 April 2021 to 11 April 2021 (non-warlike), ending in aeromedical evacuation.
Occupational History
As an RAAF aircraft technician the veteran maintained and repaired aircraft on bases in Australia and on deployment, working shifts on flight lines in heat, noise and fuel and hydraulic fluid exposure. Deployment requires compliance with a mandatory pre-deployment health and immunisation schedule, including vaccines directed by Defence for the operational environment.
During the COVID-19 pandemic Defence members deploying overseas were required to complete COVID-19 vaccination before departure, using the vaccine supplied by Defence at the time. Deployed members rely on role 1 and role 2 facilities and coalition hospitals, where specialist haematology services and specialised laboratory tests may not be available.
History
Veteran DR, an RAAF aircraft technician, received an adenovirus vector COVID-19 vaccine as a mandatory pre-deployment requirement on 23 March 2021 and developed vaccine-induced thrombotic thrombocytopenia with cerebral venous sinus thrombosis on non-warlike service in the Middle East on 02 April 2021. The condition worsened when heparin was given in theatre before the diagnosis was recognised.
Timeline
- 22 Mar 2021 — At the veteran's pre-deployment medical examination she was well, with no headache, no history of thrombosis or heparin exposure and no bleeding tendency. A full blood count showed a platelet count of 245 x 10^9/L and normal haemoglobin. She was certified fit to deploy to the Middle East on 01 April 2021, subject to completing COVID-19 vaccination. "fit to deploy, platelets 245"
- 23 Mar 2021 — As a mandatory requirement for her deployment, the veteran received a first dose of the ChAdOx1 nCoV-19 adenovirus vector COVID-19 vaccine (Vaxzevria) at the base health centre. She had mild fever and arm soreness for 36 hours, which settled. She flew to the Middle East on 01 April 2021. "ChAdOx1 dose 1, pre-deployment"
- 05 Apr 2021 — At the role 1 facility on her deployed air base the veteran reported three days of severe, constant headache, worse lying down, unrelieved by paracetamol, with nausea. It was attributed to jet lag, heat and dehydration, and she was given oral fluids and analgesia. No blood count was taken and she returned to work. "severe headache, attributed to dehydration"
- 08 Apr 2021 — The veteran had a generalised seizure on the flight line and was transferred to a coalition hospital. CT venogram showed thrombosis of the superior sagittal and right transverse sinuses. Platelets were 42 x 10^9/L, D-dimer above 20 mg/L and fibrinogen 1.2 g/L. Anti-PF4 testing was not available. She was treated with unfractionated heparin for presumed cerebral venous sinus thrombosis. "CVST, platelets 42, heparin started"
- 10 Apr 2021 — Forty hours after heparin was started the veteran became drowsy with left-sided weakness. CT showed a right temporal haemorrhagic venous infarct and extension of the sinus thrombosis, and abdominal CT showed new portal vein thrombosis. Platelets had fallen to 19 x 10^9/L. Heparin was stopped. The treating physician recorded clinical worsening and arranged aeromedical evacuation, which took place on 11 April 2021. "haemorrhagic infarct, platelets 19, worsening"
- 12 Apr 2021 — At a tertiary hospital in Australia a haematologist found a strongly positive anti-PF4 ELISA (optical density 2.8) and a positive platelet activation assay, and diagnosed vaccine-induced thrombotic thrombocytopenia with cerebral venous sinus and portal vein thrombosis. She was treated with intravenous immunoglobulin, dexamethasone and argatroban, then transitioned to apixaban. Platelets recovered to 168 x 10^9/L by 24 April 2021. "anti-PF4 positive, VITT confirmed"
- 14 Oct 2021 — Follow-up MRI venography showed partial recanalisation of the superior sagittal sinus and a persisting right temporal gliotic scar. A neurologist diagnosed structural epilepsy with focal seizures and commenced levetiracetam. She had persisting headaches, left hand weakness and fatigue and did not return to deployable duties. "structural epilepsy, partial recanalisation"
Symptoms
At onset the veteran had a severe, constant headache, worse lying down and on straining, with nausea, unrelieved by simple analgesia. She later developed a generalised seizure, and after the haemorrhagic infarct she had drowsiness and left-sided weakness.
After onset she had recurrent headaches, focal seizures, left hand weakness and clumsiness, and marked fatigue. She now reports weekly headaches, occasional focal seizures despite levetiracetam, reduced grip and fine motor control in the left hand, poor concentration, and the need for long-term anticoagulation, which restricts her work and activities.
Imaging
- 08 Apr 2021 — CT brain and CT venogram: "Thrombosis of the superior sagittal sinus and right transverse sinus. No haemorrhage."
- 10 Apr 2021 — CT brain and CT abdomen: "New right temporal haemorrhagic venous infarct with extension of the transverse sinus thrombosis into the sigmoid sinus. New thrombosis of the main portal vein."
- 13 Apr 2021 — MRI brain and MR venography: "Extensive superior sagittal, right transverse and sigmoid sinus thrombosis. Right temporal haemorrhagic venous infarct with surrounding oedema."
- 14 Oct 2021 — MRI brain and MR venography: "Partial recanalisation of the superior sagittal sinus. Persisting right transverse sinus occlusion. Right temporal gliosis with haemosiderin staining."
Onset Date
The most likely date of onset of this condition is 02 Apr 2021.
At that date the veteran was a serving RAAF flight sergeant who had arrived the day before at an air base in the Middle East on non-warlike service. Ten days after her pre-deployment ChAdOx1 COVID-19 vaccination she developed a severe, constant headache, the first symptom of the cerebral venous sinus thrombosis.
This date is appropriate because her pre-deployment examination on 22 March 2021 recorded no symptoms and a normal platelet count, and on 05 April 2021 she reported three days of severe headache. Cerebral venous sinus thrombosis with thrombocytopenia was confirmed on 08 April 2021, and the anti-PF4 antibodies on 12 April 2021 confirmed vaccine-induced thrombotic thrombocytopenia. Onset at day 10 after an adenovirus vector vaccine is typical. The date falls within continuous full-time service, and she had had no heparin exposure in the previous 30 days.
For the vaccine factor, the 100 days before onset run from 23 Dec 2020 to 02 Apr 2021, and the veteran received the ChAdOx1 nCoV-19 vaccine on 23 March 2021, ten days before onset.
For the worsening factor, the documented worsening was on 10 Apr 2021, when the haemorrhagic infarct, extension of the sinus thrombosis and portal vein thrombosis developed and platelets fell to 19 x 10^9/L. From onset on 02 Apr 2021 to that date she was in theatre, where the condition was not recognised on 05 April, anti-PF4 testing was unavailable and heparin was given from 08 April 2021.
1. What is the formal diagnosis of the condition claimed above?
The formal diagnosis is Vaccine-Induced Thrombotic Thrombocytopenia (ICD-10-AM D69.5, with the external cause of a COVID-19 vaccine), with cerebral venous sinus thrombosis and portal vein thrombosis, under the Statements of Principles concerning vaccine-induced thrombotic thrombocytopaenia, Balance of Probabilities No. 34 of 2022 and Reasonable Hypothesis No. 33 of 2022.
Vaccine-induced thrombotic thrombocytopenia is a rare immune disorder in which antibodies against platelet factor 4 activate platelets after vaccination with an adenovirus vector COVID-19 vaccine, causing thrombosis together with a low platelet count. It usually begins 4 to 30 days after vaccination, and the thromboses typically occur in unusual sites such as the cerebral venous sinuses and the portal and splanchnic veins. Features include a markedly raised D-dimer, low fibrinogen and positive anti-PF4 antibodies. Heparin and platelet transfusion can worsen it, and treatment is with intravenous immunoglobulin and a non-heparin anticoagulant. Complications include venous infarction, intracerebral haemorrhage, seizures and death.
The diagnosis followed a mandatory pre-deployment ChAdOx1 COVID-19 vaccination on 23 March 2021. It began on 02 April 2021, on non-warlike service in the Middle East, was confirmed by anti-PF4 testing on 12 April 2021 and worsened on 10 April 2021 after heparin was given in theatre.
2. For each diagnosis identified, please also provide the following dates:
When did the veteran first experience symptoms attributable to this condition?
02 April 2021.
When did the veteran first present to a health / medical provider for this condition?
05 April 2021.
When was the condition confirmed / formally diagnosed?
12 April 2021.
When did the veteran first present to you (or your practice) for this condition?
09 September 2025.
3. How was this diagnosis confirmed? i.e. what were the key symptoms and signs, investigation results, specialist opinions?
The diagnosis was confirmed by a haematologist on 12 April 2021. The veteran had thrombosis of the cerebral venous sinuses on CT venography on 08 April 2021 in association with a low platelet count of 42 x 10^9/L, and she had had no exposure to heparin within the 30 days before onset, meeting the Statement of Principles definition of vaccine-induced thrombotic thrombocytopaenia. The diagnosis was supported by a D-dimer above 20 mg/L, a low fibrinogen of 1.2 g/L, a strongly positive anti-PF4 ELISA and a positive platelet activation assay.
Onset 10 days after an adenovirus vector COVID-19 vaccine, thrombosis in the typical unusual sites of the cerebral venous sinuses and later the portal vein, and recovery of the platelet count with intravenous immunoglobulin and non-heparin anticoagulation all confirm the diagnosis. The worsening was confirmed on 10 April 2021 by a fall in platelets to 19 x 10^9/L, extension of the sinus thrombosis, a haemorrhagic venous infarct and new portal vein thrombosis on CT.
4. What do you consider to be the cause(s) of the condition in this veteran? Give consideration to constitutional and common risk factors, pre-existing injuries or diseases, and occupational or lifestyle risks, as well as direct causative mechanisms.
Legislation: the clinical onset of this condition was on 02 April 2021, after 1 July 2004, during continuous full-time service. This is a Military Rehabilitation and Compensation Act 2004 (MRCA) claim and the Statements of Principles apply. The Balance of Probabilities instrument applies to peacetime service, including the vaccination given at the base health centre in Australia on 23 March 2021 as a Defence requirement. The Reasonable Hypothesis instrument applies to the veteran's non-warlike service in the Middle East, for which the vaccination was a mandatory pre-deployment requirement, and during which both the onset on 02 April 2021 and the worsening on 10 April 2021 occurred.
Each factor must be related to the person's relevant service. Under the beneficial approach required by the legislation, the absence of documentation does not mean that an event or exposure did not occur: lack of evidence is not evidence of lack.
Balance of Probabilities — Statement of Principles concerning Vaccine-Induced Thrombotic Thrombocytopaenia, No. 34 of 2022
Causative factors
Factor 8(1): having received an adenovirus vector coronavirus disease 2019 (COVID-19) vaccine within the 100 days before the clinical onset of vaccine-induced thrombotic thrombocytopaenia; — MET
- On 23 March 2021 the veteran received a first dose of ChAdOx1 nCoV-19 (Vaxzevria), an adenovirus vector COVID-19 vaccine, at the base health centre in Australia, administered by Defence as a mandatory condition of her deployment. This was ten days before onset on 02 April 2021, well within the 100 days before onset, from 23 December 2020 to 02 April 2021.
Worsening factors
Factor 8(2): inability to obtain appropriate clinical management for vaccine-induced thrombotic thrombocytopaenia. — MET
- When the veteran presented with severe headache on 05 April 2021 no blood count was taken, and when cerebral venous sinus thrombosis with thrombocytopenia was found on 08 April 2021 anti-PF4 testing, haematology advice and intravenous immunoglobulin were not available, and she was treated with unfractionated heparin. On 10 April 2021 platelets fell to 19 x 10^9/L and she developed a haemorrhagic venous infarct, extension of the thrombosis and portal vein thrombosis. Under Brew v Repatriation Commission (1999) this is an inability to obtain appropriate clinical management.
Reasonable Hypothesis — Statement of Principles concerning Vaccine-Induced Thrombotic Thrombocytopaenia, No. 33 of 2022
Causative factors
Factor 8(1): having received an adenovirus vector coronavirus disease 2019 (COVID-19) vaccine within the 100 days before the clinical onset of vaccine-induced thrombotic thrombocytopaenia; — MET
- The ChAdOx1 nCoV-19 vaccine was given on 23 March 2021 specifically as a mandatory pre-deployment requirement for the veteran's non-warlike service in the Middle East, which began on 01 April 2021. Onset occurred on 02 April 2021, ten days after vaccination and on the second day of that operational service.
Worsening factors
Factor 8(2): inability to obtain appropriate clinical management for vaccine-induced thrombotic thrombocytopaenia. — MET
- On non-warlike service in the Middle East from 02 to 11 April 2021 the veteran could not obtain recognition of the condition, anti-PF4 testing, haematology advice, intravenous immunoglobulin or a non-heparin anticoagulant. She was given heparin, and the condition worsened on 10 April 2021 with a haemorrhagic venous infarct, extension of the thrombosis, portal vein thrombosis and a fall in platelets to 19 x 10^9/L.
The % contribution of the causes is 100% and significant.
Sequelae
The vaccine-induced thrombotic thrombocytopenia has caused cerebral venous sinus thrombosis, a right temporal haemorrhagic venous infarct, structural epilepsy, left upper limb weakness, chronic post-thrombotic headache and portal vein thrombosis, and has required long-term anticoagulation. Each of these should be considered as a sequela of the accepted condition.
Unintended Consequence
Met. The condition is an unintended consequence of the ChAdOx1 nCoV-19 vaccination provided by the Commonwealth on 23 March 2021 as a mandatory requirement for deployment, and its worsening is an unintended consequence of the unfractionated heparin given in theatre from 08 April 2021 (section 6A of the DRCA and the equivalent provisions of the MRCA).
Inability to Attain Appropriate Medical Management
MET. On deployment the veteran's severe headache on 05 April 2021 was attributed to dehydration without a blood count, and when cerebral venous sinus thrombosis with a platelet count of 42 x 10^9/L was found on 08 April 2021, anti-PF4 testing, specialist haematology advice, intravenous immunoglobulin and non-heparin anticoagulants were not available, so she was treated with heparin. Within 40 hours her platelets fell to 19 x 10^9/L and she developed a haemorrhagic venous infarct and portal vein thrombosis. Applying the objective and subjective tests in Brew v Repatriation Commission (Full Federal Court, 10 September 1999, Merkel J), the unavailability of the indicated investigation and treatment in an operational setting, through no fault of her own, amounts to an inability to obtain appropriate clinical management.
5. Please provide a Health Summary and a medication / prescribing history.
See attached report.
References
- 22 Mar 2021, Pre-deployment medical examination and full blood count, Medical Officer
- 23 Mar 2021, Immunisation record, Base health centre
- 05 Apr 2021, Role 1 treatment record, Medical Officer, Middle East
- 08 Apr 2021, Emergency admission, CT venogram and pathology, Coalition hospital, Middle East
- 10 Apr 2021, Inpatient progress notes and CT brain and abdomen, Coalition hospital, Middle East
- 11 Apr 2021, Aeromedical evacuation record, Aeromedical evacuation team
- 12 Apr 2021, Haematology consultation, anti-PF4 ELISA and platelet activation assay, Haematologist
- 13 Apr 2021, MRI brain and MR venography, Radiologist
- 14 Oct 2021, Neurology review and MRI, Neurologist
- Statement of Principles concerning Vaccine-Induced Thrombotic Thrombocytopaenia (Balance of Probabilities) No. 34 of 2022, Repatriation Medical Authority
- Statement of Principles concerning Vaccine-Induced Thrombotic Thrombocytopaenia (Reasonable Hypothesis) No. 33 of 2022, Repatriation Medical Authority
