Paper and Threads

The J and J PAUSE is over after more vaccination data was collected, analyzed, and discussed at length at the CDC-ACIP meeting on April 23rd.  These clots are now called thrombosis with thrombocytopenia syndrome (TTS) and there are now a total of 15 well studied cases which means that this is a very rare adverse effect of the vaccine.  All of the cases were in women (13 in 18-49 years of age and 2 who were 50+).  Cerebral venous sinus thrombosis (CVST) occurred in 12 of the patients, the others had other large vein clots.  Nearly 8 million people were vaccinated with the J and J vaccine since it was approved making the risk of TTS 0.7-1.6 cases/million vaccinations.  There was a significant discussion of the benefit of the vaccine vs the risk and the ACIP independent advisory board of scientists then voted to lift the PAUSE.  Having an effective vaccine that only requires one dose and no special storage requirements means that many groups of people that are house bound, in shelters, in jails, or in rural areas or other countries will be able to be vaccinated.  

The types of clots that occurred after the vaccine occurs in other situations.  Patients who develop Covid-19 actually have a higher risk of developing the clots.  There is also a substantial risk of the same clots without either the vaccine or Covid-19:   

     CVST with Covid-19     5-6 cases/million 

     CVST 2 weeks after Covid-19 diagnosis  39 cases/million (hospitalized patients)

     CVST without known associated trigger  14.5-28.5/million US population per year   See Below

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The committee recommended that a Warning be added to the Vaccine Information.  Women who are 18-49 years old can elect to get one of the mRNA vaccines to reduce their risk.  Physicians will be provided with formation to make a prompt diagnosis when patients develop a severe headache, abdominal or leg pain, or shortness of breath.  A platelet count should be obtained and if <150,000 immediate treatment with intravenous IgG and a non-heparin anticoagulant should be started.  The diagnosis should be confirmed with a PF4 antibody assay, but treatment should begin before the results are obtained.  Physicians also need to be cautioned that patients should not be given heparin  or platelets This newly described clotting process appears to be an immune response to the vaccine and resembles a rare clotting disorder that occurs in patients being treated with heparin.  No other underlying risk factors were identified among the cases.   

Posted by Shirley at 6:28 AM | Permalink | Comments (0)

I have a guest contributor today - my son Jason - who is a Pediatric Hematologist-Oncologist.  He has a daily Instagram post with family photos of the day (for us I hope - to see our 2 grandchildren) and a paragraph about the pandemic.  This was his science paragraph from yesterday.

"A terrific study was published today in Nature (one of the pre-eminent scientific research journals) that details the very health care issues faced by people who get even mild cases of COVID.  The study looked at non-hospitalized VA patients, comparing over 73,000 who were diagnosed with COVID to nearly 5 million who were seen for non-COVID reasons.  And the top line result is that in the 6 months following their diagnoses. the COVID patients had an increased risk of death, respiratory disease and failure, clotting disorders, neurocognitive disorders, diabetes and hypertension, among a number of other conditions.  In addition, those who had COVID used more pain medications (both opioid and non-opioid), antidepressants, and cardiac medications.  More Below

All in all, it is sobering, because it is a real-world look at what people might face if they get COVID (even mild or asymptomatic).  And it is a massive wake-up call about the importance of doing everything we can do to avoid getting COVID - mild or severe, there's a very real chance that you'll spend months or more dealing with the consequences.  So keep wearing your mask around others and indoors, get vaccinated, and help those in your life make good choices and get their vaccine appointments.  We can do this! "

Posted by Shirley at 11:54 AM | Permalink | Comments (0)

We know the efficacy of the mRNA Vaccines from Phase 3 trials, and now we can look at Breakthrough Cases to assess "real world" effectiveness.  A breakthrough case is defined as a Covid-19 positive patient who developed Covid-19 more than 2 weeks after their 2nd vaccine dose or single dose of J and J vaccine.  This week the CDC published data on 5,814 breakthrough cases  collected from Dec. 14 - April 13.  These infections are expected to occur because no vaccine is 100% effective.  But in science it is always important to know the denominator!    As of April 13th 75 million people were vaccinated in the US, but how many of them had 2 doses and were more than 2 weeks out from their final dose.  The CDC relies on State reporting systems for breakthrough cases and only 43 States reported cases.  Of the cases reported, we don't know how many  of them had a sample for genomic sequencing for variants.  The data is probably underestimated and not helping to determine true incidence and protection against variants due to incomplete reporting and lack of original samples to identify variants that are spreading.

The cases were from 43 States, 45% were 6O years or older, 65% were women, and 34% were asymptomatic making it hard to know how the cases were even identified.  Three hundred and ninety-six patients were hospitalized, and 74 died.  From now on the CDC will modify their "breakthrough case" surveillance to those patients who are hospitalized or die - in order to get the most important information.  See Below  

Another recent report to illustrate the value of the denominator: 6 women who received the J and J vaccine, 6-13 days before, developed CVST (cerebral vein sinus thrombosis) with thrombocytopenia (low platelets).  One patient died and only 2 already left the hospital.  All of the patients had a positive platelet factor 4 (PF4) test to detect the autoantibody that may be causing these clots/low platelets.  Approximately 6.8 million doses of J and J vaccine had been administered to date in the US (risk 1:1 million).  But is the denominator really 6,800,000 or half that to determine the risks in those vaccinated within the month before the diagnosis of the clots, or only in the women vaccinated during that time period?  Each time we decrease the denominator the risk increases. Then to confuse the science even more, there is also a risk of CVST in Covid-19 patients because CVST occurs in unvaccinated Covid-19 patients as well.  Will the Risk vs Benefit ratio of the J and J vaccine be enough to continue using it?  The CDC ACIP Committee will meet again on Friday.

Posted by Shirley at 6:14 AM | Permalink | Comments (0)

Evaluating a Headache After Vaccination with J and J and AstraZeneca Vaccines:  The rare clotting adverse event after vaccination with one of the two adenovirus viral vaccine vaccines is now being called vaccine-induced thrombotic thrombocytopenia (VITT).  I am a retired hematologist and have evaluated many patients with blood clots - venous and arterial - and in general the development of a cerebral venous sinus thrombosis (CVST) in very rare.  But the US Vaccine Adverse Effect Reporting System (VAERS) for monitoring vaccine safety demonstrated 6 cases, all associated with low platelets. This combination resembles a heparin side effect known as Heparin-Induced Thrombocytopenia (HIT) - in which patients on heparin develop antibodies to a complex known as heparin-PF4 (platelet factor 4).  I spent the first 15-20 years, after my training, in a lab purifying, characterizing, and then measuring PF4. Since then a test has been developed to measure the heparin-PF4 antibodies in patients with HIT.  Now these tests are found to also be positive in patients with VITT following the J and J and AstraZeneca vaccines, even though none received heparin 

Some Risk Factors for any Clots: OCP, pregnancy, malignancy, smoking, immobility, inherited disorders.  

Risk Factors for CVST: J and J Vaccine: 1 per million;  Covid-19 4-20 per 100,000; pregnancy 10-20 per 100,000 deliveries; oral contraceptives 2.7-40 per 100,000 people, and General Population: 3-15 per million per year.

The risk factors and incidence for development of CVST shows that the incidence for VITT is substantially less than the incidence in patients with Covid-19.  With the current data, the risk vs benefit ratio warrants continuation of J and J vaccinations, maybe to select age groups.  

The CDC-FDA still have a PAUSE on J and J vaccinations - to carefully study any patients that may develop clots within 3 weeks after their vaccination that was before the pause.  Patients who develop severe headaches, abdominal pain, leg pain or shortness of breath should see a physician and have an evaluation - including a platelet count and a PF4 antibody test.  Under no circumstances should patients with clot, low platelets, and a positive PF4 test be treated with heparin - instead consult a hematologist for alternate treatments.   

Posted by Shirley at 6:31 AM | Permalink | Comments (0)

Yesterday we learned that there would be a PAUSE in the administration of the Johnson and Johnson vaccine in order for the CDC and FDA to carefully review 6 cases of unusual blood clots associated with thrombocytopenia (decreased platelets).  The blood clot is in the veins of the brain (called central venous sinus thrombosis - CVST) or even more rarely in the veins in the abdomen.  The CDC and FDA together decided to PAUSE while they carefully studied these patients, one of whom died. The incidence of this type of clot in unvaccinated patients is 2-14 per million patients,  In this study there were 6 cases in almost 7 million J & J vaccinations in the US. or a risk of 1 per million.  What makes this CVST different is the severely decreased platelet count that occurs with it. 

Patients with CVST develop severe headaches, abdominal pain, leg pain, or shortness of breath and should consult a physician. This is not the flu-like headache seen 1-2 days after vaccination. The 6 women were between the ages of 18-48 and the onset of the thrombosis occurred 6-13 days after the vaccination.  A complete blood count should be done in addition to imaging studies to identify the clot and document the decreased platelet count.  Patients with venous clots are usually treated with heparin, but it is contraindicated in these patients - which is one of the reasons that the CDC and FDA wanted to PAUSE the vaccinations so physicians could be alerted to the possible diagnosis and correct treatment.  See Below

Scientists want to see if they can identify any underlying risk factors, or specific patient groups that should not get the J&J vaccine.    Oral Contraceptive drugs did not seem to be the common factor.  At this time it appears as if this syndrome is due to the development of autoimmune antibodies, which activate the platelets and cause clotting.  These same types of clots, with thrombocytopenia, is also found after the AstraZeneca vaccines and groups of scientists here and abroad are already studying these events and changes in the coagulation system.  Note: both the J and J vaccine and Oxford-AstraZeneca vaccines use a harmless adenovirus to carry the spike protein DNA into cells so spike protein can be made and stimulate an immune response.  Pfizer and Moderna are messenger RNA vaccines - a different platform for vaccine production. 

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