Polikarpov ITP

Polikarpov ITP

Polikarpov ITP

The Polikarpov ITP was a promising design for a cannon-armed fighter that was delayed by problems with the different engines used to power it and that never entered production.

The ITP was designed around two unproven water-cooled inline engines - the Klimov M-107 and the Mikulin AM-37. Two prototypes were built, the M-1 powered by the M-107 and the M-2 powered by the AM-37, but both engines proved to be unreliable.

The ITP was a low-wing monoplane, with a wooden monocoque fuselage and metal wings. The wing was made up of a centre section and two outer panels (the same configuration as on the Polikarpov I-16), and was fitted with flaps and automatic slats. The centre section contained honeycomb radiators, with the air intakes in the wing leading edge and the exhausts towards the back of the upper wing surface. The exhaust outlets could be used to provide some extra thrust.

The prototype M-1 was armed with one engine mounted SkK 37mm cannon and wing mounted 20mm cannon, justifying its name - Istrebitel Tyazhely Pushechny or Fighter, Heavy Gun. Later it was rearmed with a 20mm cannon in the nose. The aircraft could also carry four 100kg bombs or eight RS-82 rockets under the wings.

The M-1 prototype made its maiden flight on 23 February 1942 at Novosibirsk. The unreliable M-107 engine repeatedly disrupted the test programme, and towards the end of the year was replaced with the M-107A. The modified aircraft was then used for static tests and structural testing, so never flew again. The aircraft had an estimated top speed of 382mph or 400mph with the extra boost from the exhaust.

The M-2 prototype was built around the AM-37 engine, and was armed with three 20mm cannon. This engine was if anything less reliable than the M-107, and had to be replaced with a 1,600hp AM-39 engine before the aircraft made its maiden flight. This came on 23 November 1943, but the flight test programme didn't begin until the summer of 1944. In tests the modified M-2 prototype had a top speed of 403mph, a service ceiling of 37,700ft but a disappointing rate of climb.

The modified M-2 was on a par with the best Soviet single seat fighters, but it offered little if any advantage over the aircraft already in production, while Polikarpov's designs were no longer in favour. As a result the ITP never entered production.


Polikarpov ITP

In 1941, the Polikarpov OKB began work on an Istrebitel' Tyazhely Pushechny - heavy cannon fighter - which was to mount a 37mm cannon between the cylinder banks of a 1,650hp Klimov M-107P 12- cylinder liquid-cooled Vee engine, and also carry two synchronised 20mm cannon. The aircraft was of mixed construction, the fuselage being a wooden monocoque and the wing of steel and dural. The first prototype, referred to as the M-1, was completed in October 1941, but difficulties with the engine delayed the initiation of flight testing until 23 February 1942. An M-107A replaced the M-107P late in 1942, but engine difficulties were still experienced, and a second prototype, the M-2, was completed with an AM-37 engine of 1,400hp with which it flew on 23 November 1943. The M-2 had an armament of three 20mm cannon and eight RS-82 unguided rocket projectiles, the engine eventually being replaced by an AM-39 of 1,700hp. Factory flight testing continued until June 1944 when the programme was abandoned.

The 37mm cannon had a very slow rate of fire. Aiming was said to be difficult.


ITP (M-1 and M-2), N.N.Polikarpov

D uring the Great Patriotic War N.N.Polikarpov made an effort to design a fighter with performance even with best contemporary machines, but with superior firepower. He chose liquid-cooling engines of new design from both V.Ya.Klimov and A.A.Mikulin, promising high power output.

Airframe of the ITP was similar to I-185. Wooden monocoque fuselage made of multi-layer birch ply was combined with duralumin wing (main spar had steel shelves), controls - with fabric cover. Oil cooler located in 'chin' position. Water cooler - in the wing, with intakes on the leading edge. Heavy Sh-37 cannon fired through the propeller hub, pair of synchronized ShVAK cannons were also housed under the engine cowling.

Jean Alexander notices 'strange reminiscence' between the ITP and Mikoyan-Gurevich MiG-1/MiG-3. Actually this is not a surprise, because both designs are rooted in the N.N.Polikarpov 'Kh' (Cyrillic 'X') project of high-altitude interceptor.

1969" by Heinz J.Nowarra and G.R.Duval, p.315
Last one may be found also at "History of aircraft construction in the USSR", Vol.2 p.187

First variant (M-1) was assembled in October 1941 and was flown first time on February 23, 1942. In 1942 VK-107P engine was replaced with VK-107A.


Contents

In November 1940, Nikolai Polikarpov proposed a heavy cannon-armed fighter for bomber escort duties and ground attack missions. The new ITP was designed around either the 1,230 kW (1,650 hp) Klimov M-107P or the Mikulin AM-37 inline engines. Two armament configurations were planned. The first consisted of a 37-millimetre (1.5 in) cannon firing through the propeller hub and two synchronized 20-millimetre (0.79 in) ShVAK cannon mounted on each side of the fuselage nose. The 37 mm cannon was provided with 50 rounds and the ShVAK had 200 rounds each. The second configuration substituted an additional ShVAK with 200 rounds for the 37 mm cannon. [1] It had racks for eight unguided RS-82 rockets underneath the wings. [2]

The ITP was a low-wing, mixed construction monoplane with a wooden monocoque fuselage made from 'shpon', molded birch plywood. The two-spar metal wing was built in three sections with automatic leading edge slats. The engine radiators were built into the wing center section with intakes in the wing roots while the oil cooler was located under the engine. The curved, one-piece windshield lacked a flat front panel which gave the pilot a rather distorted view. The conventional undercarriage, including the tailwheel, was fully retractable. [1] It carried 624 litres (137 imp gal 165 US gal) of fuel in tanks between the spars of the wing center section. The rear fuselage, cockpit and tail resembled that of the Polikarpov I-185. [2]

The first ITP prototype (M-1) was completed in October 1941 with a 1,300-horsepower (970 kW) M-107P engine. Due to German attacks, the aircraft was evacuated to Novosibirsk and did not make its first flight until 23 February 1942. The M-107P engine proved unreliable and was changed to a M-107A in late 1942. The 37 mm gun was deleted in exchange for another 20 mm gun mounted on the side of the fuselage. Flight testing was not completed because the airframe was used for ground static testing, [3] but the estimated maximum speed at 6,300 metres (20,669 ft) was 655 km/h (407 mph) with a time to 5,000 metres (16,404 ft) of 5.9 minutes. [2]

The second ITP prototype (M-2) was built in 1942 and fitted with a Mikulin AM-37 engine which also proved unreliable and was replaced with a 1,345 kW (1,800 hp) Mikulin AM-39 that December. It first flew on 23 November 1943 but the manufacturer's flight tests were not completed until June 1944. Since several other aircraft with about the same level of performance were already available, it was not placed into production. [4]


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Here we have sleek and fast heavy fighter/ground attack airplane from Polikarpov in the form of the ITP M-1 prototype.

AG-1 - 20mm ShVAK cannons
AG-2 - 37mm Sh-37 cannon

History:
The ITP was designed around two unproven water-cooled inline engines the 1,650 hp Klimov M-107 and the 1,400 hp Mikulin AM-37. Two prototypes were built, the M-1 powered by the M-107P and the M-2 powered by the AM-37, but both engines proved to be unreliable.

The ITP was a low-wing monoplane, with a wooden monocoque fuselage and metal wings. The wing was made up of a centre section and two outer panels (the same configuration as on the Polikarpov I-16), and was fitted with flaps and automatic slats. The centre section contained honeycomb radiators, with the air intakes in the wing leading edge and the exhausts towards the back of the upper wing surface. The exhaust outlets could be used to provide some extra thrust.

The prototype M-1 was armed with one engine mounted 37mm Sh-37 cannon and upper-cowling mounted 20mm cannon, justifying its name - Istrebitel Tyazhely Pushechny or Fighter, Heavy Gun. Later, the 37mm cannon was replaced with a 20mm cannon on the port side of the nose. The aircraft could also carry four 100kg bombs or eight RS-82 rockets under the wings.

The M-1 prototype made its maiden flight on 23 February 1942 at Novosibirsk. The unreliable M-107P engine repeatedly disrupted the test programme, and towards the end of the year was replaced with the M-107A. The modified aircraft was then used for static tests and structural testing, so never flew again. The aircraft had an estimated top speed of 382mph or 400mph with the extra boost from the exhaust.

Three-view drawing of ITP (M-1).

Three somewhat-grainy photos of M-1 prototype.

Uncowled M-107P engine of M-1 prototype. 37mm cannon barrel
can be seen extending through propeller hub at far right.

M-107P engine with cowling on.

Armoured seat for ITP pilot.


Πίνακας περιεχομένων

Τον Νοέμβριο του 1940 ο Νικολάι Πολικάρποφ πρότεινε την δημιουργία ενός μαχητικού που θα ήταν οπλισμένο με πυροβόλα και θα αναλάμβανε αποστολές συνοδείας βομβαρδιστικών και εγγύς υποστήριξης. Σχεδιάστηκε με προωστικό σύστημα τον κινητήρα Klimov M-107P ή τον Mikulin AM-37. Επίσης προτάθηκαν δύο διατάξεις του οπλισμού: η πρώτη αποτελούνταν από ένα πυροβόλο των 37 mm που έβαλε μέσα από τον κώνο της έλικας και δύο συγχρονισμένα πυροβόλα ShVAK των 20 mm, ένα σε κάθε πλευρά του ρύγχους. Το πυροβόλο των 37 mm είχε αναχορηγία 50 βλημάτων ενώ τα ShVAK από 200 έκαστο. Η δεύτερη διάταξη οπλισμού προέβλεπε την χρήση ενός ακόμα ShVAK με 200 βλήματα στην θέση του πυροβόλου των 37 mm. [1] Το αεροσκάφος μπορούσε επίσης να μεταφέρει οκτώ ρουκέτες RS-82. [2]

Το ITP ήταν ένα χαμηλοπτέρυγο αεροσκάφος, μικτής κατασκευής. Η άτρακτος ήταν κατασκευασμένη από ξύλο και οι πτέρυγες από μέταλλο. Το σύστημα προσγείωσης ήταν πλήρως ανασυρόμενο. [1] Μπορούσε να μεταφέρει μέχρι και 624 λίτρα καυσίμου. Το πίσω μέρος της ατράκτου, το πιλοτήριο και το ουραίο ήταν παρόμοια με του Polikarpov I-185. [2]

Το αρχικό πρωτότυπο (Μ-1) ολοκληρώθηκε τον Οκτώβριο του 1941 με κινητήρα Μ-107P ισχύος 1300 hp. Για να προστατευθεί από την γερμανική προέλαση το Σχεδιαστικό Γραφείο μεταφέρθηκε στο Νοβοσιμπίρσκ με συνέπεια την καθυστέρηση πολλών προγραμμάτων. Το ITP πραγματοποίησε τελικά την παρθενική του πτήση στις 23 Φεβρουαρίου 1942. Ο Μ-107P αποδείχθηκε αναξιόπιστος και αντικαταστάθηκε από τον M-107A στα τέλη του έτους. Το πυροβόλο των 37 mm αντικαταστάθηκε τελικά από ένα των 20 mm. Οι πτητικές δοκιμές δεν ολοκληρώθηκαν διότι το ίδιο αεροσκάφος χρησιμοποιούνταν και για στατικές δοκιμές. [3] Σύμφωνα με τις εκτιμήσεις θα μπορούσε να φτάσει μέγιστη ταχύτητα 655 km/h σε ύψος 6300 m και θα χρειάζονταν 5,9 λεπτά για να φτάσει σε ύψος 5000 m. [2]

Το δεύτερο πρωτότυπο (Μ-2) κατασκευάστηκε το 1942 με κινητήρα Mikulin AM-37, που επίσης αποδείχθηκε αναξιόπιστος και αντικαταστάθηκε στην συνέχεια από τον Mikulin AM-39 των 1,800 hp. Πραγματοποίησε την παρθενική του πτήση στις 23 Νοεμβρίου 1943 αλλά οι πτητικές δοκιμές ολοκληρώθηκαν τον Ιούνιο του επόμενου έτους. Όταν το ITS ήταν έτοιμο, η αεροπορία διέθετε ήδη αεροσκάφη με παρόμοιες ή καλύτερες επιδόσεις και έτσι το μαχητικό δεν μπήκε σε παραγωγή. [4]


Thrombocytopenia following Pfizer and Moderna SARS-CoV-2 vaccination

Eun-Ju Lee, Department of Medicine, Division of Hematology New York Presbyterian Hospital – Weill Cornell, 1305 York Ave, 7 th floor New York, NY 10065.

Division of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

Division of Hematology, University of Washington, Seattle, Washington

Division of Hematology/Oncology, Georgetown University Medical Center, Lombardi Comprehensive Cancer Center, Washington, District of Columbia

Centre Hospitalier Universitaire Henri-Mondor, Université Paris Est Creteil, Creteil, France

The Bleeding and Clotting Disorders Institute, University of Illinois College of Medicine-Peoria, Peoria, Illinois

Division of Hematology and Transfusion Medicine, Lund University, Lund, Sweden

Department of Medicine, Michael G. DeGroote School of Medicine, McMaster Centre for Transfusion Research, McMaster University, Hamilton, Ontario, Canada

Centre Hospitalier Universitaire Henri-Mondor, Université Paris Est Creteil, Creteil, France

Division of Hematology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania

Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania

Division of Pediatric Hematology/Oncology, New York Presbyterian Hospital – Weill Cornell, New York, New York

Division of Hematology, New York Presbyterian Hospital – Weill Cornell, New York, New York

Eun-Ju Lee, Department of Medicine, Division of Hematology New York Presbyterian Hospital – Weill Cornell, 1305 York Ave, 7 th floor New York, NY 10065.

Division of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

Division of Hematology, University of Washington, Seattle, Washington

Division of Hematology/Oncology, Georgetown University Medical Center, Lombardi Comprehensive Cancer Center, Washington, District of Columbia

Centre Hospitalier Universitaire Henri-Mondor, Université Paris Est Creteil, Creteil, France

The Bleeding and Clotting Disorders Institute, University of Illinois College of Medicine-Peoria, Peoria, Illinois

Division of Hematology and Transfusion Medicine, Lund University, Lund, Sweden

Department of Medicine, Michael G. DeGroote School of Medicine, McMaster Centre for Transfusion Research, McMaster University, Hamilton, Ontario, Canada

Centre Hospitalier Universitaire Henri-Mondor, Université Paris Est Creteil, Creteil, France

Division of Hematology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania

Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania

Division of Pediatric Hematology/Oncology, New York Presbyterian Hospital – Weill Cornell, New York, New York

Cases of apparent secondary immune thrombocytopenia (ITP) after SARS-CoV-2 vaccination with both the Pfizer and Moderna versions have been reported and reached public attention. Public alarm was heightened following the death of the first identified patient from an intracranial hemorrhage, which was reported on the Internet, then in USA Today 1 and then in The New York Times. 2 Described below, we have collected a series of cases of very low platelet counts occurring within 2 weeks of vaccination in order to enhance our understanding of the possible relationship, if any, between SARS-CoV-2 vaccination and development of ITP with implications for surveillance and management.

Twenty case reports of patients with thrombocytopenia following vaccination, 17 without pre-existing thrombocytopenia and 14 with reported bleeding symptoms prior to hospitalization were identified upon review of data available from the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), agencies of the U.S. Department of Health and Human Services (HHS) Vaccine Adverse Events Reporting System (VAERS), published reports, 3, 4 and via direct communication with patients and treating providers. These cases were investigated as suspicious for new onset, post-vaccination secondary ITP we could not exclude exacerbation of clinically undetected ITP. Search terms relating to “decreased platelet count”, “immune thrombocytopenia”, “hemorrhage”, “petechiae”, and “contusion” were utilized to identify cases reported in VAERS.

The reports describing 19 of 20 patients included age (range 22–73 years old median 41 years) and gender (11 females and 8 males). Nine received the Pfizer vaccine and 11 received the Moderna vaccine. All 20 patients were hospitalized and most patients presented with petechiae, bruising or mucosal bleeding (gingival, vaginal, epistaxis) with onset of symptoms between 1–23 days (median 5 days) post vaccination. Platelet counts at presentation were available for all 20 cases with the majority being at or below 10 × 10 9 /L (range 1–36 × 10 9 /L median 2 × 10 9 /L).

One patient had known ITP in remission another had mild–moderate thrombocytopenia in 2019 with note of positive anti-platelet antibodies, a third had previous mild thrombocytopenia (145 × 10 9 /L) while a fourth had inherited thrombocytopenia with baseline platelet counts of 40–60 × 10 9 /L. Three other patients had known autoimmune conditions including hypothyroidism, Crohns disease, or positive tests for anti-thyroglobulin antibodies. Treatment for suspected ITP was described in 15 of the cases, including corticosteroids n = 14, intravenous immune globulin (IVIG) n = 12, platelet transfusions n = 8, rituximab n = 2, romiplostim = 1, vincristine = 1, and aminocaproic acid (Amicar) n = 1 combination therapy was used in most patients. Initial outcomes were reported in 16 cases. An improvement in the platelet count was described in patients treated with platelet transfusion alone (n = 1), corticosteroids alone (n = 1), corticosteroids + platelet transfusion (n = 3), corticosteroids + IVIG (n = 3), corticosteroids + IVIG + platelet transfusion (n = 5), corticosteroids +IVIG + rituximab + vincristine + romiplostim (n = 1). The index patient passed away after a cerebral hemorrhage, as mentioned, notwithstanding having received emergent treatment with IVIG, steroids, rituximab and platelet transfusions. Another patient had no improvement in platelet counts after 3 days, but treatment details are not specified.

Five additional patients with ”thrombocytopenia” or ”immune thrombocytopenia” post vaccination were identified in VAERS (last accessed 2/5/21), but either available information is insufficient for inclusion or the clinical scenarios suggest alternative processes contributing to thrombocytopenia. One 59 year-old man was identified with ”thrombocytopenia” at an unspecified time after receiving the Pfizer vaccine without additional details regarding platelet count, clinical course, or treatment. A 44 year-old woman was hospitalized for nausea, vomiting and chest pain on the day that she received the Pfizer vaccine. Her laboratory values included a platelet count of 85 × 10 9 /L and a peak troponin level of 4 ng/mL (normal < = 0.04 ng/mL). The patient was diagnosed with myocarditis but did not require treatment for thrombocytopenia. Her platelets were 61 × 10 9 /L on discharge, but subsequent platelet counts were not reported. The third is a patient without age or gender reported who was found to have thrombocytopenia, neutropenia and a pulmonary embolism at an unspecified time following the Pfizer vaccine. This patient was hospitalized and passed away no additional details were available. A fourth patient, a 37-year-old man, had ”thrombocytopenia requiring hospitalization, meds and platelet infusion” 4 days following the Moderna vaccine with no details regarding presenting symptoms, platelet count, treatment or outcome. The last patient is an 80 year-old man with multiple medical problems including recent transcatheter aortic valve replacement, hypothyroidism, and diverticulosis who presented 6 days after the Pfizer vaccine with bloody diarrhea, hemoglobin 8.7 g/dL and platelets 60 × 10 9 /L. He received several units of packed red blood cells and two units of platelets with improvement to 101 × 10 9 /L and was discharged 5 days later. There were a handful of reports with minimal additional details alluding to a male who passed away in December from brain hemorrhage following the Pfizer vaccine – these could be describing the index patient. We did not attempt to obtain information on patients with pre-existing active ITP who received a SARS-CoV-2 vaccine for this report.

We identified additional reports of post-vaccination bruising or bleeding unrelated to the injection site, but no mention of platelet counts, or thrombocytopenia, was provided. Note, VAERS was last accessed on January 29, 2021 for this search. Fourteen patients reported ”petechiae”/”bruising” of whom three were evaluated in the office and one presented to the emergency room. There have been 51 reports of” bleeding”/”hemorrhage” (vaginal n = 11, conjunctival n = 13, cerebral n = 6, gingival n = 2, gastrointestinal n = 5, epistaxis n = 12, and cutaneous n = 2). There were 31 patients who did not seek additional evaluation, seven were seen via office visits, while 13 presented to the emergency room or were hospitalized. Two patients passed away in the hospital. No additional details are available.

Are these case of primary ITP coincident with or secondary ITP as a result of vaccination? In either case, the clinical presentations and the favorable response to “ITP-directed” therapies in most of the treated patients, such as corticosteroids and IVIG suggest an antibody-mediated platelet clearance mechanism that is operative in ITP.

Is the relationship between vaccination and thrombocytopenia coincident or causal? It is not surprising that 17 possible de novo cases would be detected among the well over 20 million people who have received at least one dose of these two vaccines in the United States as of February 2, 2021. This would be less than one case in a million vaccinated persons, consistent with the absence of cases seen in the more than 70 000 subjects enrolled in the combined Pfizer and Moderna vaccine trials. 5, 6 If we assume that these reports identify 17 cases of secondary ITP that developed following vaccination, this extrapolates to 17 × 6 (because only cases that occurred during the first 2 months [December 2020 – January 2021] following vaccine rollout are captured) × 15 to cover the fraction of the population that has been vaccinated [20 million of the 300+ million total US population]) = approximately 1500 cases of post-vaccine secondary ITP/year. There are approximately 50 000 adults who are diagnosed with ITP in the US each year. If we explored the temporal relationship of the 17 cases occurring within 1-2 weeks of vaccination, then we could extrapolate by multiplying by 26 or 52 weeks to look at the rate of ITP per year if the cases are totally ‘coincidental’. This would be approximately 39,000 to 78,000 cases of ITP per year which is not far from the estimated total baseline incidence per year. Thus, the incidence of an immune-mediated thrombocytopenia post SARS-CoV-2 vaccination appears either less than or roughly comparable to what would be seen if the cases were coincidental following vaccination, perhaps enhanced somewhat by heightened surveillance of symptomatic patients. These estimates are very rough so this information should be considered very preliminary. It also assumes that all cases of clinically significant ITP are reported.

The incidence of secondary ITP following other types of vaccines provides an inconsistent picture. It is estimated that approximately 1:40 000 children develop secondary ITP after receiving measles-mumps-rubella (MMR) vaccine. 7 Well-documented cases of acquired immune thrombocytopenia have been reported after varicella and other vaccinations as well, including one described in this issue of the American Journal of Hematology following Shingrix recombinant Zoster vaccine. 8-10 On the other hand, the only case–controlled study of adult recipients of all vaccines published 10 years ago was interpreted as indicating no discernable increase in ITP within 1 year post vaccination. 11 In the absence of pre-vaccination platelet counts and given the variable time post vaccination to discovery of thrombocytopenia, it is impossible to precisely estimate the incidence of secondary ITP post SARS-CoV-2 vaccination at this time. However, it is notable that all but one of the cases identified thus far occurred after the initial dose of SARS-CoV-2 vaccine. One would assume that if the vaccination was unrelated to development of ITP, case occurrences would divide more evenly between the two doses. It is also likely that the actual incidence of thrombocytopenia, including mild asymptomatic cases, may be higher and go unreported.

Even in view of the uncertain relationship between SARS-CoV-2 vaccination and secondary ITP, it is worth considering possible mechanisms by which this might occur. Thrombocytopenia has been reported after treatment with some anti-sense oligonucleotides, 12, 13 but it would seem that a far higher, sustained level of RNA reaching dendritic cells in lymph nodes and elsewhere would be required to generate an immune response than is likely seen based on a single intramuscular injection. This is also inconsistent with the very rapid onset of thrombocytopenia in the index and additional cases.

Another possibility is that some individuals may have pre-formed antibodies, including those directed against poly-ethylene-glycol or to other components of the outer lipid layer of the nanoparticles. This presumes that antibodies directed against a novel antigen formed by attachment of vaccine particles on a small number of platelets trigger a reaction involving “all” platelets, which seems unlikely. Recent articles identified antibodies detected post Covid-19 infection that activated platelets 14 and an ITP-like syndrome following natural infection 15, 16 both findings require confirmation and the relationship to the post vaccination ITP cases reported here is uncertain.

Third, some patients may have had mild “compensated” thrombocytopenia of diverse causes, for example, pre-existing ITP or hereditary thrombocytopenia. For example, one of the patients reported in this issue of the American Journal of Hematology had a documented borderline platelet count (145 × 10 9 /L) 2 months prior to receipt of the vaccine raising the question of pre-existing subclinical ITP. 3 The other patient reported in this issue of the American Journal of Hematology had chronic, hereditary thrombocytopenia, with a last known exacerbation 12 years prior to the present episode. 4 An additional patient identified in VAERS had platelets of 55–115 × 10 9 /L in 2019. Severe thrombocytopenia in these patients or others may have been induced by enhancement of macrophage-mediated clearance or impaired platelet production as part of a systemic inflammatory response to vaccination. 8, 17 This is compatible with patients in whom severe thrombocytopenia was first noted 1–3 days post-vaccination. Transient drops in platelet counts post vaccinations for influenza and other viruses is a not uncommon observation in patients with ITP and other causes of thrombocytopenia.

Lastly, post-vaccination ITP remains possible, especially in those with onset 1-2 weeks after exposure. One patient in our series had a normal platelet count documented in the week prior to receipt of the vaccine and only developed symptomatology 13 days post vaccination compatible with vaccine related secondary ITP.

The reported cases also provide insight into diagnosis and treatment. Most of the patients responded to treatment with corticosteroids and IVIG but showed little benefit from platelet transfusion, a pattern consistent with that of ITP. There was no response in the two patients treated with rituximab but they were only evaluable for up to 2 weeks in addition, rituximab would impair the response to vaccination, if given within days to 2 weeks of the vaccination and for at least 4-6 months subsequently. The first of two patients (with sufficient information available) continued to have a platelet count of 1–2 × 10 9 /L and died of intracranial bleeding 16 days post vaccination and 13 days post presentation of ITP despite receiving platelet transfusions, steroids, IVIG, and rituximab. The second patient presented 1 day after vaccination and still had a count of 1 × 10 9 /L 7 days later despite receiving the same combination of the four ITP treatments however, she responded following addition of vincristine and romiplostim. The suggestion might be (from this very limited information) to give IVIG and high dose steroids as initial treatment. If this does not work and the platelet count remains very low, it would seem appropriate to institute other treatments within the first week including a thrombopoietic agent perhaps starting above the lowest dose often recommended to initate therapy and potentially vinca alkaloids depending upon response. Excluding rituximab from initial treatment seems appropriate in most cases given that response can take up to 8 weeks 18 and response to vaccination can be impaired. Once a platelet response is seen, patients could be managed as if they were typical cases of primary ITP. Whether such cases will prove to be self-limiting or persist and lead to chronic ITP remains uncertain.

In summary, we cannot exclude the possibility that the Pfizer and Moderna vaccines have the potential to trigger de novo ITP (including clinically undiagnosed cases), albeit very rarely. Distinguishing vaccine-induced ITP from coincidental ITP presenting soon after vaccination is impossible at this time. Additional surveillance is needed to determine the true incidence of thrombocytopenia post vaccination. If the incidence of thrombocytopenia post vaccination is higher than that based on available case reports, we anticipate that many more cases will be reported in the coming weeks as a higher proportion of the population is vaccinated. It may be worthwhile to see whether exacerbations of other conditions considered to have an autoimmune pathophysiology occur as well to gain a better understanding of host response to vaccination.

Notwithstanding these concerns, the incidence of symptomatic thrombocytopenia post vaccination is well below the risk of death and morbidity from SARS-CoV-2 infection as also described on the Platelet Disorder Support Association (PDSA) website in the statement from the Medical Advisory Board. We echo recommendations from the PDSA and the American Society of Hematology that strongly encourage reporting this and other potential complications through VAERS and in any other way deemed appropriate. Finally, we recommend immediately checking a platelet count in anyone who reports abnormal bleeding or bruising following vaccination and consulting a hematologist.

Management of vaccination in patients with pre-existing ITP is complex and is not explored here. The opinion of the Medical Advisory Board of PDSA is that in most, but not necessarily all, patients the benefit of vaccination exceeds the risk of exacerbating ITP. At this time, for patients with ITP it appears reasonable to obtain a baseline count before vaccination and then obtain additional platelet count(s) following vaccination based on patient clinical and treatment history. In patients who present with severe thrombocytopenia soon after vaccination in the absence of other likely causes, we believe it would be appropriate to pursue aggressive treatment for presumed ITP. Whether to administer a second dose of vaccine or whether a change to a different vaccine is warranted in patients who develop thrombocytopenia or substantial worsening of pre-existing thrombocytopenia with the initial dose requires further study.


Idiopathic Thrombocytopenic Pupura: A History

Idiopathic Thrombocytopenic Purpura (ITP) is a misnomer. The rare condition causes antibodies to destroy platelets important for blood clotting, and can produce symptoms of low platelet count, unusual haemorrhaging, including intracranial haemorrhage (rare but potentially life threatening), mucosal and gingival haemorrhaging, abnormal menstruation, petichiae, purpura and a general propensity to bruise easily.

However, some patients may remain asymptomatic other than a low platelet count. Acute and spontaneously resolving occurrences are more commonly seen in children, whilst adult onset ITP is more likely to be chronic. The terminology assigned to the disorder has changed and evolved over time, reflecting increased understanding of the mechanisms of ITP through medical and scientific advancements. The issue of the misnomer stems from our increased knowledge – as it turns out, ITP is generally not “Idiopathic”, and purpura is not seen in all patients.

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Early history

Medicine has a long held fascination for ITP. Stasi and Newland’s ITP: a historical perspective, notes a number of potential examples of ITP, the first dating back almost a thousand years. A description by Avicenna of purpura with characteristics of ITP can be found in the 1025 The Canon of Medicine.

In 1556 a case of spontaneously resolving purpura and bleeding is reported by Portuguese physician Amatus Lusitanus in the book Curationum Medicinalium Centuriae. Lazarus de la Riviere, physician to the King of France proposes in 1658 that purpura is a phenomenon caused by a systemic bleeding disorder.

In 1735 Paul Gottlieb Werlhof, a German physician and poet, provides us with the first detailed description of a case of ITP, which subsequently becomes known as Werlhof’s disease.

Controversies

Controversy arises regarding the mechanisms of thrombocytopenia, with Frank in 1915 suggesting it is the result of suppression of megakaryocytes by a substance produced in the spleen, alternatively Kaznelson purports thrombocytopenia is due to increased destruction of platelets in the spleen.

In 1916, Kaznelson persuades a professor to perform a splenectomy on a patient with chronic ITP, the outcome of which is a startling postoperative increase in the patient’s platelet count and resolution of purpura. Splenectomy becomes the prevailing treatment for those with refractory ITP for many years.

The Harrington-Hollingsworth experiment

Self-experimentation in medicine is considered by some to be a historical tradition, and preferable to the unethical treatment of patient subjects, the extremes of which can be seen in examples such as the Tuskegee Syphilis Experiment. The self-experimentation undertaken in the Harrington -Hollingsworth experiment was risky for the participants, but is a good example of experimentation that could not be undertaken ethically on research subjects.

In 1950 Harrington and Hollingsworth, who were hematology fellows at Barnes Hospital in St Louis, endeavored to test their idea that the cause of ITP was a factor in blood that destroyed platelets. Harrington, who happened to match the blood type of a patient being treated at the hospital for ITP, received a 500ml transfusion of the patient’s blood.

Hours after the procedure Harrington’s platelet count plummeted, and he had a major seizure. Bruising and petichiae became conspicuous over four days of low platelet count, improvement not noted until five days later.

On examination of Harrington’s bone marrow, no effect on megakaryocytes could be deduced. This suggested an effect on the platelets, rather than the marrow. The experiment was replicated on all viable members of the hospital’s hematology department, with all recipients of plasma from patients with ITP experiencing a decrease in platelet count within 3 hours of transfusion.

The legacy of Harrington-Hollingsworth experiment, along with other reports published in 1951, led not only to new understanding of the disorder, but also a name change: idiopathic thrombocytopenic purpura became immune thrombocytopenic purpura.

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Evolution of treatment

The increased understanding of ITP as an autoimmune disorder led to the development of treatments other than splenectomy. Corticosteroids were introduced in the 1950’s, and since the 1960’s a number of immunosuppressive agents have been utilised, however the evidence for their efficacy is somewhat lacking.

Intravenous immunoglobulin (IVIG) as a treatment for ITP was first trialed in 1980 on a 12 year old boy with severe, refractory ITP, with the result of an increased platelet count within 24 hours, and continued increases upon further daily IVIG administrations.

Pilot studies ensued, with results establishing the efficacy of IVIG therapy in increasing platelet counts in ITP patients. IVIG consumption, not only for the treatment of ITP but for various hematologic, inflammatory and autoimmune diseases, has increased world-wide since 1980 from 300kg per year to 1000 tonnes per year in 2010. Alongside corticosteroid therapy, IVIG remains a first line treatment for ITP, particularly in patients at high risk for bleeding or preoperatively.

Currently, second line therapy includes use of immunosuppressants, corticosteroid-sparing agents, monoclonal antibodies, splenectomy, thrombopoietin receptor agonists and vinca alkaloids. We have come a long way since Werlhof’s apparent cure of ITP with citric acid!

The 1980’s also saw new evidence arise regarding platelet destruction in ITP by investigators at the Puget Sound Blood Centre. Further studies were able to demonstrate the inhibition of megakaryocyte growth and maturation in vitro, of antibodies from ITP patients.

More recently an international working group has established two major diagnostic categories of ITP, Primary ITP, where other conditions of thrombocytopenia are excluded, and Secondary ITP in which the condition is due to infection by other diseases and bacterias, for example HIV or hepatitis C.

Further, categories have been established to assist with the approach to management of ITP, including newly diagnosed ITP, where the diagnosis is less than three months old, persistent ITP where diagnosis is between three and twelve months old and the condition has not spontaneously resolved, chronic ITP lasting longer than twelve months, and severe ITP, described as bleeding at presentation requiring treatment, or new bleeding symptoms which demand additional treatment with a different platelet enhancing therapy or increased dosage of current therapy.

Current understanding of Idiopathic Thrombocytopenic Purpura

The pathogenic causes of ITP remain little understood, but a multifaceted etiology is suspected. The role of eradication of Helicobacter pylori in raising platelet counts of ITP patients has recently been explored, with a considerable variability found in response to H.pylori eradication from country to country.

This high variation may be due to differences in strains of H.pylori internationally, with Japanese strains being frequently CagA-positive, and American strains usually CagA-negative. Increased platelet responses due to eradication of H.pylori are higher in patients with the CagA-positve strain of the bacteria.

Personal blogs of individuals with ITP are also providing doctors and other medical professionals with greater insights into possible causes of the condition.

Massive leaps in the treatment and management of ITP have been achieved within the last hundred years, though clearly there are still gaps in the understanding of its pathogenesis. Treatment for refractory ITP failing first and second line treatments is an area that may still yield improvements. Greater understanding and management of the course of ITP means more patients are treated appropriately.


Contents

The original request for proposals for a heavy escort fighter (Tyazholyy Istrebitel' Soprovozhdeniya) was received at the Polikarpov OKB in November 1938, but the press of work with the I-180 and SPB prototypes prevented any significant design work until the third quarter of 1940. Mikhail Yangel was appointed head designer, but his job was complicated by multiple changes in the role of the aircraft from escort fighter to interceptor, dive bomber, and eventually reconnaissance. [1]

The prototype, internally designated as aircraft or TIS "A", was a low-wing, all-metal, cantilever monoplane with two Mikulin AM-37 engines and a twin tail. The monocoque fuselage had four 7.62 mm (0.300 in) ShKAS machine guns in the nose, each with 1,000 rounds. The pilot and the gunner/radio-operator were seated back-to-back, separated by an armor plate, under sliding canopies. The gunner had a dorsal ShKAS on a TSS-1 mount with 750 rounds that could be used once his canopy was slid forward. He also had a ventral ShKAS mounted below the armored floor that he could access by raising a hatch in the floor and kneeling down to fire the machine guns. The ventral gun was provided with 500 rounds of ammunition. A 12.7 mm (0.50 in) UBK machine gun with 400 rounds and a 20 mm (0.79 in) ShVAK cannon with 350 rounds were mounted in each wing root. [2] Underneath the wings were two racks each capable of carrying a single 500 kg (1,100 lb) FAB-500 bomb. The wing had automatic leading edge slats and four split flaps separated by the engine nacelles. The single wheel landing gear retracted into the rear part of the nacelles, as did the tailwheel into the fuselage. [3]

The 'A' prototype first flew in September 1941 and reached a speed of 555 km/h (345 mph) at 5,800 m (19,000 ft) altitude. It suffered from a lack of directional stability and the engines were unreliable and vibrated above 5,000 m (16,000 ft). Factory No. 51 attempted to fix the stability problem in late September by increasing the area of the rear fins, but was unsuccessful. Flight testing continued in October in Novosibirsk, to where the LII (Russian: Лётно-исследовательский институт—Flight Research Institute) had been evacuated. Eliminating the stability problem took until March 1942, although the engines remained as unreliable as ever. [4]

By the summer of 1942 it was clear that the Mikulin OKB lacked the resources to fix the problems with the AM-37 and that the TIS would need a new engine, but the OKB's resources were fully utilized on the I-185 and ITP programs and the TIS program was put on hold. Work did not resume on the TIS until the second half of 1943, after the I-185 had been canceled, and the Mikulin AM-39 engine was selected. A new prototype was built, internally called the "MA", with a completely revised armament. Two ShVAK cannon replaced the nose ShKAS machine guns and a UBT machine gun in a VUB-1 mount replaced the dorsal ShKAS, while the ventral machine gun was removed entirely. Two 37 mm (1.5 in) Shpitalny Sh-37 or 45 mm (1.8 in) 111P cannon replaced the wing root guns. The intended AM-39s were unavailable and therefore two Mikulin AM-38Fs were used as a temporary expedient. The engine radiators were moved from the nacelles into the wings. [5] They were fed by inlets in the leading edge and outlets on the undersurface of the wing. [5]


History of ITP

In 1970 Red Burns saw a demonstration of the Sony portapak. A filmmaker by training, she realized that the new accessibility of videotape was going to radically change who could tell their story in her medium of motion pictures. An activist by temperament, Red intuited that this new tool should get into the hands of the people.

The transforming technologies of the day have changed from videotape to disc storage to personal computers to the web and physical computing but the mission has stayed the same - getting students to ask how can those technologies could enrich the lives of ordinary people. How can they improve society? Not just making life easier, safer and more efficient but more just, more beautiful, more meaningful and more fun. We have put the new technical possibilities into creative hands of thousands of alumni from every possible background and watched what emerges. By way of that process we have have helped shaped some of the most important changes of our times.

Of course these platforms are now commonplace, combined into something small and affordable that fits in your pocket. But first they spent years as crazy ideas being played with and developed at places like ITP. We fully expect that some of the crazy ideas bouncing around ITP now will one day look perfectly normal and find their way into everyday life. The best is yet to come.

Red Burns Scholarship Fund

There is no better way to honor Red Burns’ life and work than to help us keep ITP alive and well by donating to the Red Burns Scholarship Fund. We are seeking to raise $5 million dollars, which will serve as a solid base to build the future of ITP. We are well on our way to our goal, thanks to the alumni contributions at the 30th and 40th anniversary celebrations. Your contributions to the Red Burns Scholarship Fund will keep ITP within the reach of the best and the brightest students, from all over the world, from diverse backgrounds and who will continue to discover and make an as yet unimagined future.


Watch the video: IL2 1946 Polikarpov ITP